Beth Bell, MD, MPH

CDC microbiologist Brian Yoo prepares a panel of isolates. Photo: CDCThe threat of antibiotic resistance (AR) is a growing challenge around the world. Antibiotic-resistant germs—bacteria that no longer respond to the drugs designed to kill them—cause more than 2 million illnesses and 23,000 deaths each year in the United States alone. It is critical for scientists and researchers to be equipped with the right tools and the best information available to combat antibiotic resistance and improve antibiotic use. Better diagnostic tests are needed to help us characterize and identify resistant pathogens—an important component of diagnosing an infection early and accurately, and preventing spread of resistant infections. And new antibiotics are needed to more effectively treat infections with bacteria that have already developed resistance. One of the new resources available to researchers is the Antimicrobial Resistance Isolate Bank (AR Isolate Bank), which was launched in 2015 by the US Centers for Disease Control and Prevention (CDC). An AR isolate panel is removed from the freezer. Photo: CDC A collaboration between CDC and the US Food and Drug Administration (FDA), the AR Isolate Bank is a curated repository of nearly 400 unique AR pathogens pulled from CDC’s collection of more than 450,000 AR isolates and more than 18,000 characterized genomes. These curated isolate collections—called panels—provide researchers with well-characterized, resistant bacteria that can be used to develop effective and accurate next-generation diagnostics and accelerate research for new antibiotics. E.coli. Photo: CDC A timely example of the value of the AR Isolate Bank panels is its collection of E.coli isolates with the mcr-1 gene. Increasing reports of bacteria carrying mcr-1 genes have put public health experts across the globe on high alert. These genes can make bacteria containing them resistant to the crucial antibiotic colistin—a last resort drug being used to treat “nightmare bacteria” carbapenem-resistant Enterobacteriaceae. Within three weeks of identification of E.coli with the mcr-1 gene in the United States, the CDC assembled appropriate panels for the bank. Public health, industry, academic, and private labs can use these panels to calibrate their diagnostic tests so that they can ensure that bacteria carrying the mcr-1 gene are quickly and accurately identified and characterized. Findings from these calibrated tests will help public health partners ramp up targeted detection and response. The sample isolates can also help researchers build new tests to detect these types of resistance in the future—all to more quickly slow the spread of resistance.Since the launch of the AR Isolate Bank, more than 140 customers—including academic, commercial, federal, hospital and clinic, and public health laboratories—have requested panels. CDC is collaborating with FDA to support and expand use of this resource. At this time, the isolates are only available for shipment to recognized US laboratories with confirmed biosafety officers.The AR Isolate Bank is one small piece of CDC’s wide-ranging work to reduce the spread and impact of antibiotic resistant infections. CDC’s Antibiotic Resistance Solutions Initiative supports implementation of the surveillance, prevention, and stewardship activities outlined in the National Action Plan for Combating Antibiotic-Resistant Bacteria, which identifies critical actions to be taken by federal agencies to combat the emergence of resistant bacteria.

In this guest post, Beth P. Bell, MD MPH—director of the National Center for Emerging and Zoonotic Infectious Diseases at the US Centers for Disease Control and Prevention (CDC)—discusses the growing problem of antibiotic drug resistance and what we can do to address this challenge. The spread of drug-resistant tuberculosis could undermine advancements in HIV and AIDS prevention. Photo: CDC. I am pleased to have the opportunity to write about what is perhaps today’s most vexing public health challenge—the growing threat of antibiotic resistance. Super-resistant bacteria have become a worldwide crisis. In India, 58,000 babies died in 2013 of an infection with resistant bacteria usually passed on from the mother during childbirth. In Thailand, 38,000 people die each year from “superbug” infections. And the numbers are only slightly better in the European Union, which loses 25,000 people each year, or in the United States, which annually attributes 23,000 deaths and two million illnesses to antibiotic-resistant infections. Currently, global health faces enormous challenges from both well-established epidemics like HIV and AIDS and malaria and new epidemics like Ebola and pandemic influenza. But antibiotic-resistant infections are steadily spreading across the globe and could soon eclipse them all. Unfortunately, this is not an apocalyptic fantasy but a real and growing threat. But the good news is that we can do something about antibiotic resistance and, like most public health problems, the more we collaborate today, the more we mitigate the threat tomorrow. Turning the tide on the “superbugs” requires a coordinated international response from all sectors. It will be especially critical for international non-governmental organizations and global foundations to build and support portfolios of work in this area and to collaborate with the World Health Organization (WHO), CDC, and other international partners to stop this threat. The threat of antibiotic resistance is two-fold: it creates infections that are untreatable, and it undermines the progress that we have made in other areas of public health and healthcare improvement. Not surprisingly, drug-resistant infections result in costlier treatments, extended hospital stays, and higher mortality. They also can dismantle some of our most significant public health achievements. For example, the benefits of antiretroviral therapies, which have saved countless lives of people with HIV and AIDS across the globe, may be negated by the burden of drug-resistant tuberculosis, gonorrhea, and other resistant infections to which people with HIV and AIDS are more vulnerable. Increasing global travel further compounds the problem by making it easy for drug-resistant germs to spread across borders and oceans. The new reality is that all countries, regardless of the sophistication of their medical care, have become vulnerable to these infections. The United States has both imported and exported drug-resistant threats. The first outbreak of carbapenem-resistant Enterobacteriaceae (CRE)—the “nightmare bacteria” that are resistant to most available antibiotics—occurred in New York City. From there, the infection migrated to France by way of an infected US traveler. Another type of CRE known as New Delhi Metallo-beta-lactamase (NDM) was first identified in South Asia, then introduced to other parts of the world, including the United States, by infected travelers. Once established in a new country, these resistant bacteria often become endemic in communities and healthcare environments. Many current NDM infections are in patients with no travel history. Developed countries have been working to define the scope and address antibiotic-resistant threats inside their borders. In many developing countries, the ability to accurately estimate the burden of antibiotic resistance or know what forms of resistance are evolving is even more limited. The CDC is working globally to increase investments in combatting antibiotic-resistance bacteria through bilateral partnerships, such as the Global Health Security Agenda, as well as via multilateral efforts in partnering with WHO. But we need your help. We need your partnership to help us reduce antibiotic resistance around the world. A top priority is ensuring that countries everywhere have sustainable healthcare infrastructures, because the lesson of Ebola is that a vulnerability in one country can become a vulnerability in our country. Now it’s time to join together and focus on how we can help countries strengthen basic capacities and provide the tools they will need to defeat antibiotic resistance. This includes: Laboratory detection of antimicrobial resistance—Countries need medical laboratory infrastructure to diagnose the cause of infections and to identify the best drugs for treatment. We also need to invest in rapid diagnostics to guide appropriate antibiotic use and identify which antibiotics will be effective. We need rapid and easy-to-use diagnostic tests that can distinguish between infections that do or do not require antibiotics. This will reduce unnecessary antibiotic use. National antibiotic resistance tracking programs—Countries need the infrastructure to collect resistance data from hospital laboratories and report these data in national and global surveillance reports. These data are necessary to: Drive appropriate prevention interventions. Develop policies that support prevention efforts. Measure the impact of prevention efforts. Antibiotic stewardship programs—We need to work collaboratively globally to ensure that antibiotics are available to treat infections, while at the same time making certain that antibiotic use is appropriate to limit the development of new forms of resistance. Infection control programs—Improving hygiene and infection control practices in healthcare settings is critical for preventing the transmission of antibiotic-resistant pathogens between patients and between hospitals, and the benefits extend to other global infectious disease threats such as Ebola, Middle East Respiratory Syndrome (MERS), and emerging infectious diseases. Healthcare environments and poor infection control are major drivers of antibiotic resistance. Technologies that improve infection control have the potential to significantly reduce infection rates. This is especially important in low resource environments—how to best support hand washing where there is a lack of clean water and how to best deploy rapid diagnostics that can work, like dipsticks and other technologies that don’t require electricity.

In this guest post, Beth P. Bell—director of the National Center for Emerging and Zoonotic Infectious Diseases—and Tom Kenyon—director of the Center for Disease Control and Prevention’s (CDC) Center for Global Heath—write about a new initiative from the US government to address global health security. The US government’s recent commitment to global health security recognizes that health security is an essential part of every nation’s national security. As both Department of Health and Human Services Secretary Kathleen Sebelius and CDC Director Tom Frieden have said, “A health threat anywhere is a health threat everywhere.” These threats may come from naturally occurring disease outbreaks, the emergence of drug-resistance, or by the intentional or accidental release of dangerous pathogens. They may occur anywhere on the planet at any time. Mitigation of such threats is greatly enhanced when the nations in which they may arise are able to detect them early, respond rapidly, and prevent them from happening again—or better still, from happening in the first place. In February, the United States joined with 28 other countries, the World Health Organization (WHO), and 3 other international organizations to launch the Global Health Security Agenda. At the launch, the United States made a commitment to working with 30 countries over the next 5 years to establish and strengthen their abilities to prevent, detect, and respond to infectious disease threats. In fiscal year (FY) 2014, a group of 12 nations will accelerate engagement in these global health security strengthening partnerships with US agencies. Pending additional resources, more countries will be added in FY 2015 and beyond. Global health security is embodied in a comprehensive set of specific targets to prevent, detect, and respond to infectious disease threats. These objectives are based in part on the WHO’s revised International Health Regulations (IHR (2005)) which established core requirements for monitoring public health threats globally and responding rapidly and effectively to contain them. Although adopted by nearly every nation on earth, fewer than 20 percent of Member States who signed on to the IHR (2005) are in full compliance. One of the major objectives of the US government’s global health security effort is to greatly increase IHR compliance. Partner countries will develop systems, policies, and procedures to prevent or mitigate outbreaks. Prevention priorities include: Monitoring and slowing antimicrobial resistance (AR), the ability of bacterial and viral pathogens to acquire resistance to antimicrobial drugs. Nations should have at least one reference laboratory able to identify—and to report—at least three of the seven WHO priority AR pathogens using standardized detection assays. Practices and policies to prevent animal diseases from spilling over into human populations. Immunization of at least 90 percent of each nation’s 1-year-olds with at least one dose of measles vaccine (or a combination vaccine including measles). Having this capacity means a nation is able to adequately carry out other immunization and health-care efforts. The United States will also work with countries to create and strengthen real-time networks of information systems to detect outbreaks, and up-to-date rapid diagnostic tests to enable their laboratories to conduct at least five of 10 core tests for high-risk and high-priority diseases. Six of these core tests are for diseases that are among the WHO Top 10 Causes of Death in low-income countries: influenza virus, poliovirus, HIV, tuberculosis, malaria, and typhoid fever. The remaining four tests will be selected by the partner country based on national public health concerns. Other priorities will strengthen countries’ abilities to detect global disease threats including: Surveillance for potential public health emergencies. Interconnected electronic reporting systems. Training for doctors, veterinarians, biostaticians, lab scientists, and field epidemiologists. The United States will also assist partner countries to develop skills and build systems to mount effective responses to health threats. These include establishing emergency operation centers (EOCs) with rapid-response teams and linkage to a network of labs that monitor for disease outbreaks. The goal is for an EOC to be able to activate a coordinated response within two hours of detecting a public health emergency. Nobody knows where the next health threat will arise. In a world linked by international travel and commerce, no nation is more than a plane flight away from any other. Global health security is a key element of every country’s national health security. For more information, please visit CDC’s global health security website at http://www.cdc.gov/globalhealth/security/.

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