Research Roundup: new discoveries in the search for a malaria vaccine and tuberculosis treatment and lessons from the Ebola epidemic

The National Institute of Allergy and Infectious Diseases (NIAID) announced last week that two experimental Ebola vaccines appear to be safe for widespread use, based on early results of clinical trials in Liberia. NIAID will now expand its trials to include as many as 1,500 volunteers, testing the vaccine candidates for efficacy. Volunteers will receive either the vaccine candidate developed by GlaxoSmithKline, another developed by NewLink Genetics Corp, or a placebo. Researchers will examine the immune response to the vaccines to see if participants develop antibodies against Ebola. None of the participants will be intentionally exposed to the Ebola virus. Scientists at NIAID have identified several genetic conditions that affect one’s risk for malaria, and which primarily manifest as red blood cell abnormalities. The researchers followed 1,543 children in Mali for three years, during which time they recorded 4,091 cases of malaria. Genetic disorders that either decreased the production of hemoglobin—the protein that transports oxygen in the blood—or led to the creation of hemoglobin C, an abnormal form of the protein, were associated with increased risk for malaria. Two genetic traits—HbAS and homozygous X-linked G6PD deficiency—appear to protect against malaria. The HbAS gene was not only associated with lower risk for malaria, but with less severe cases of malaria in children who contracted it. Researchers at Cornell University have mapped the genome of Ancylostoma ceylanicum, one of two species of hookworm that infect humans. The study identified 31,000 different genes, including those that are active in hookworms during infection. Scientists believe that as many as 70 of those genes could be promising targets for new drugs or vaccines, and plan to start testing experimental vaccines in hamsters this year.

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.