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The US Department of Health and Human Services has published new rules intended to improve compliance to a 2007 law intended to increase the public availability of clinical trial data. The law requires researchers to register and share data from clinical trials, grants the US Food and Drug Administration (FDA) the authority to fine pharmaceutical companies up to US$10,000 per day for failure to register or report results, and allows the US National Institutes of Health (NIH) to refuse to disburse funds to noncompliant grantees. Between 2008 and 2015, violations of the law warranted more than $25 billion in fines, however, no such fines have been issued to date. Many advocates have expressed concern that the new rules are only as effective as their enforcement. Neither the FDA nor the NIH plan to hire additional staff to enforce compliance of the law. Facebook CEO Mark Zuckerberg and his wife Dr. Priscilla Chan have committed US$3 billion over the next ten years to “cure, prevent, or manage all disease.” The couple is investing $600 million to launch the “Biohub” at the University of California, San Francisco, which will convene scientists and engineers, supporting collaboration in research and product development. The Biohub’s first two ventures are ambitious: the Cell Atlas, which will involve the characterization of every type of cell found in the human body, and the Infectious Disease Initiative, which will support research and development (R&D) for drugs, diagnostics, and vaccines against infectious diseases. The Initiative will establish a Rapid Response Team with the ability to rapidly mobilize scientists and accelerate R&D during an outbreak. The mosquito-borne Mayaro virus, primarily found in the Amazon, has been reported in Haiti. The symptoms of Mayaro—fever and joint pain—are similar to chikungunya, however, the pain can last for nearly a year and patients often report abdominal pain as well. The virus, which was identified in a blood sample taken from a child suffering from the illness, varied from the strain responsible for the more than 40 cases reported in South America since its discovery in 1954. Researchers are particularly concerned with the presence of Mayaro in the Caribbean in light of the ongoing outbreak of Zika virus, which was discovered several decades ago but has only recently begun to spread rapidly and have a significant health impact. A new report from the World Bank quantifying the economic impact of antimicrobial resistance (AMR) indicates that by 2050, the impact of AMR on the global economy and in particular, the livestock industry, could push nearly 30 million people into extreme poverty. Further, drug-resistant infections are much more difficult and costly to treat, and thus, AMR could increase health spending by $1 trillion per year by 2050. These findings reveal that AMR could have a much greater economic impact than the 2008 financial crisis, particularly for low- and middle-income countries. Gonorrhea, a sexually transmitted infection resulting in nearly 90 million new infections each year, has grown increasingly resistant to antibiotics. A new cluster of cases in Hawaii suggests that the emergence of untreatable strains of the bacteria are closer than ever. Over time, gonorrhea has developed resistance to several common antibiotics including penicillin, tetracycline, and fluoroquinolones; the current treatment, a combination of the antibiotics azithromycin and ceftriaxone, is considered the last resort. The samples identified in Hawaii showed unprecedented levels of resistance to azithromycin and burgeoning resistance to ceftriaxone. While azithromycin and ceftriaxone are the only remaining drugs that are effective against the bacteria and well tolerated by humans, scientists at Louisiana State University are testing a new oral antibiotic that appeared to be safe and effective against gonorrhea in phase 2 clinical trials.

Scientists have devised a Trojan horse strategy to prevent the Ebola virus from infecting human cells. To infect humans, the virus binds to the surface of a human cell, enters the cell, and then binds to the protein Niemann-Pick C1 (NPC1). Once it binds to NPC1, the virus can start replicating and spreading throughout the body. Consequently, the researchers first engineered two antibodies: one that targets the human protein NPC1 and another that targets the viral protein that binds to NPC1. However, they needed a Trojan horse: a molecule that could deliver the antibodies to the scene of the crime, deep inside human cells, where the virus binds to NPC1. The solution? The team synthesized each antibody with a third antibody that binds to the surface of the Ebola virus. In short, the team created two molecules by combining the antibody that could latch onto the virus with two antibodies that could prevent the virus from infecting human cells. Both combinations proved effective in the lab against all five strains of the Ebola virus and in mouse trials, one of the molecules effectively treated infected mice. Next, the molecules will be tested in nonhuman primates. A recent piece in STAT takes an in-depth look at the critical advances in hepatitis C research that paved the way for the development of Sovaldi, the first drug proven to cure hepatitis C. Hepatitis C was first discovered in 1989, however, the virus is notoriously difficult to reproduce in the lab. Consequently, the time and cost of producing the virus hindered research. Ralf Bartenschlager and Charles Rice, researchers at the University of Heidelberg and Rockefeller University, respectively, determined that certain mutations of the virus enabled select strains of the virus to survive in the lab, and engineered versions of the virus—deemed “replicons”—with those mutations. Using these replicons, drug companies were able to rapidly screen the efficacy of different compounds in combatting hepatitis C. Among these companies, the small biotech firm Pharmasset developed a particularly promising drug, which was eventually—after the company was acquired by Gilead Sciences—approved and marketed as Sovaldi. The drug became the first cure for Hepatitis C, however, its price tag of up to US$94,000 for the full regimen has impeded access to it. While existing evidence suggests that Zika infection has the greatest impact on fetal brain development during the first trimester of pregnancy, new research indicates that infection later in pregnancy can still have a devastating impact. Scientists at the University of Washington infected a pregnant monkey with the virus at the beginning of her third trimester, and in less than a month, significant damage to the fetus was reported: both the white matter in the brain and the head itself stopped growing. However, the team administered the virus in higher doses than would be found in individual mosquitoes, and researchers at the University of Wisconsin-Madison, who used lower doses, found no fetal brain damage after infecting four pregnant monkeys.

United Nations General Assembly. Photo: UN Photo/Loey FelipeEvery year in mid-September, the world’s diplomatic corps descends upon midtown Manhattan for two weeks of snarled traffic, road closures, and general mayhem. The cause of this paralysis? The United Nations General Assembly (UNGA)—a gathering of all the highest levels of the world’s governments to address those issues so pressing that only a global response will suffice.In recent years, global development, including global health, has featured prominently on both the UNGA formal and side-event agendas. This year the bulk of the formal agenda—set by Fiji which holds the Presidency of the General Assembly—focuses on oceans, climate change, and refugees and migration. However, the assembly also includes a full-day, high-level summit on antimicrobial resistance (AMR) scheduled by the outgoing Norwegian General Assembly President. Though other global health issues may not feature on the formal agenda, there are a number of hot topics that will certainly be highlighted at side events throughout the week. Here are the major global health policy issues GHTC will be tracking:Antimicrobial Resistance A CDC scientist studies a drug resistant strain of bacteria. Photo: James Gathany With the publication of the Review on Antimicrobial Resistance (also known as the O’Neill report), which was commissioned by government of the United Kingdom to comprehensively examine the global problem of AMR, the full scale of the human and economic cost of the rise of AMR is becoming clear. Seven hundred thousand people die each year globally from AMR infections, and the United States alone spends an extra US$20 billion on health due to AMR. As a result, global attention has focused on how best to both support development of novel antibiotics and conserve antibiotics of last resort to prevent the development of further resistance. At the full-day summit on September 21, world leaders will convene to discuss how the global community can collectively address AMR. A number of organizations are also sponsoring side events and conferences devoted to the myriad ways to stem the tide. It will remain to be seen whether any political commitments or new bilateral AMR initiatives emerge. Zika/Ebola/Pandemic preparedness/Global Health Security AgendaThe West African Ebola outbreak and the ongoing Zika pandemic have focused the world’s attention on the fundamental weakness of international pandemic preparedness efforts. With the continuing international spread of Zika, strengthening the international community’s ability to prevent, detect, and respond to outbreaks remains a global priority. The gathering of so many world leaders in one place for UNGA will create a ripe environment to foster novel partnership models to strengthen health systems to stand up to future outbreaks. While not featured on the formal agenda, a number of high-level side events on health systems strengthening and partnerships could spur interesting new initiatives post-UNGA. Access to MedicinesOn Wednesday, the United Nations Secretary-General’s High-Level Panel on Access to Medicines (HLP), convened in late 2015 by Secretary-General Ban Ki-moon, published its final report offering recommendations for “remedying the policy incoherence between the justifiable rights of inventors, human rights law, trade rules, and public health in the context of health technologies.” The issues tackled in the report and the panel’s recommendations for improving access to health technologies are highly contentious with health advocates, industry, and other trade and intellectual property stakeholders holding divergent viewpoints on how best to achieve this aim. This tension is reflected in the final report itself, which though released as a consensus document, also contains six separate commentaries by HLP members advocating positions other than those taken in the report.Given the timing of this report release, it should be a central topic of discussion at UNGA as various groups choose whether to lend their support to carrying forward the recommendations or criticize the panel for going too far or not far enough. Looking further forward, this issue will also feature prominently at a March special session of the United Nations Human Rights Council.While your author expects that these will be the key global health policy issues addressed at this year’s UNGA, there are always a few last-minute surprises. Needless to say, GHTC will keep you informed of exactly what is going on in the midst of the midtown Manhattan mayhem all week long.

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.