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Aedes aegypti mosquitoes which carry Zika. Photo: Dean Calma/IAEAApril showers bring standing pools of water, the onset of mosquito season, and a new wariness of getting bitten. In 1999, we were caught off guard when the West Nile virus first appeared in North America. In 2010, an outbreak of dengue fever spread locally in Florida after an absence of 60 years. In 2014, chikungunya first arrived in the United States after travelling breathtakingly fast through the Western hemisphere. Now, in 2016, Zika virus is the latest mosquito-borne disease to threaten Americans. Yet our collective national response continues to be one of short-term planning rather than long-term preparedness.Since Zika virus arrived in the Americas in May 2015, there has been an alarming spike in reports of birth defects such as microcephaly, particularly in Brazil. Zika infection has also been linked to adverse pregnancy outcomes and Guillain-Barré syndrome—a temporary paralysis that can prove deadly. The World Health Organization has declared Zika a Public Health Emergency.The virus has now spread to 26 countries, including 312 travel-associated cases in the United States. So far, mosquitoes in the United States haven’t infected anyone, but the Centers for Disease Control and Prevention (CDC) just issued a revised map that shows the mosquitoes that carry this virus and others can be found across the Southern tier of the United States all the way up to southern New England on the East Coast.Faced with this chilling situation, we don’t have ready the tools we need to fight Zika. Just like with Ebola, crucial tools did not exist or were still under development when the outbreak began. R&D is urgently needed to understand the Zika virus and its associated health conditions, and develop new diagnostics, vaccines, or other treatments to combat it. A pregnant woman in El Salvador receives an ultrasound as part of the country's response to the Zika outbreak. Photo: Office of the President of El Salvador Today, the Band-aid approach of emergency funding is the only option available to mitigate the crisis. We applaud President Obama’s call for accelerated research efforts, and the need to inform Americans about how to protect themselves, which the CDC has been quick to do. The National Institute of Allergy and Infectious Diseases, led by Dr. Anthony Fauci, has also called for a “full court press” on research.This requires increased funding for those searching for ways to stop this virus. Diverting resources from the Ebola response, however, is short-sighted. Those efforts are just beginning to show the promise of new diagnostics, advanced therapeutics, and more resilient health systems in Ebola-affected countries. Redirecting funding before the job is finished is dangerous, and will most certainly leave the United States and the world unprepared for the next Ebola outbreak.The fact remains that this long-standing patchwork approach to global health R&D funding only degrades our ability to respond to the guaranteed next global health crisis. With more than 500 mosquito-borne diseases across this globally interconnected world, the question is not if but when we see another virus or disease.Just as we need primed and ready firehouses and firefighters, we need a primed and ready research infrastructure. That requires a prioritized agenda and sufficient funding. America’s “firehouses and firefighters” are the National Institutes of Health, CDC, President’s Malaria Initiative and the Army and Navy’s tropical infectious disease programs.Global health means everyone’s health. It’s time US policymakers stop funding by crisis and commit to sustainable, long-term investment in global health R&D so the most effective health solutions are available when they are needed.Stephen Higgs, PhD, FRES, FASTMH is the president of the American Society of Tropical Medicine and Hygiene and a professor at Kansas State University. Erin Will Morton, MA is director of the Global Health Technologies Coalition, a group more than 25 nonprofits that work to save and improve lives by encouraging the research and development of essential health technologies.

Until very recently, no new class of antibiotics had been discovered in nearly 30 years. However, as antimicrobial resistance spreads, there is an urgent need for new antibiotics, particularly those that can treat infections resistant to existing drugs. In article in Health Affairs, Allan Coukell, senior director for health programs at the Pew Charitable Trusts, is calling on Congress to pass the Promise for Antibiotics and Therapeutics for Health (PATH) Act, which would permit the US Food and Drug Administration (FDA) to approve new antibiotics for use in limited patient populations with modified clinical trial requirements that would be determined by the agency itself. There is little financial incentive for antibiotic R&D as they are prescribed for short periods of time and as there is much competition among antibiotics. Conducting clinical trials, particularly for drug-resistant infections, is challenging: not only are these infections rare, but many patients are disqualified from participation due to compromised immune systems or pre-existing conditions. Additionally, the dearth of rapid tests results in many patients starting antibiotic regimens before being diagnosed with a drug-resistant infection. The PATH Act has passed the Senate Health, Education, Labor and Pensions Committee and was included in the 21st Century Cures Act, which passed the House of Representatives last year. Pharmaceutical company GlaxoSmithKline (GSK) announced that it will not file patents for its products in least developed and low-income countries, enabling manufacturers to produce and distribute generic versions of their medicines in 50 countries with a combined population of nearly 1 billion people. In lower middle income countries, GSK will continue to file patents but will offer ten-year licenses to generic manufacturers for a small royalty. GSK is also exploring innovative ways to increase access to its new and future cancer drugs through voluntary licensing via the Medicines Patent Pool, a United Nations–backed initiative that partners with patent holders and generic manufacturers to facilitate access to medicines. The Pool was founded in 2010, exclusively for HIV and AIDS drug patents, but has since been expanded to include tuberculosis and hepatitis C. The HIV virus mutates rapidly, and thus, standard approaches to vaccine development have not been successful. Rather, researchers have been testing and adapting antibodies—proteins targeting a specific pathogen—from patients, searching for the rare broadly neutralizing antibodies which are effective against manifold strains of the virus. Scientists at The Scripps Research Institute (TSRI) have now characterized the first “teenage” broadly neutralizing antibody, an immature version of the molecule, not yet effective against the HIV virus. The molecule was discovered by the Chinese Center for Disease Control and Prevention (China CDC). The team at China CDC collected blood samples from hundreds of HIV-positive patients, identifying those with the most effective anti-HIV antibodies. The patients were then monitored for five years, enabling the researchers to observe antibody development. Previously, scientists believed that broadly neutralizing antibodies matured over 10–15 years, however, from its teenage stage, this potent antibody developed rapidly in just 2 years. The researchers hope this discovery could inform HIV vaccine research and development by providing insight into how to prompt the human immune system to rapidly produce effective broadly neutralizing antibodies.

Aedes Aegypti mosquito which carries the Zika virus. Photo: CDC/James GathanyOn Tuesday, the Obama administration announced that it will transfer nearly US$600 million in remaining Ebola funds to fight the growing threat of Zika virus. But many questions remain. Where is the money going? From what accounts will it come? And what does this mean for the Global Health Security Agenda (GHSA) programming which is supposed to help protect against these threats in the future?In February, the President requested $1.9 billion in emergency appropriations to combat the Zika virus outbreak, but authorization was stalled by members of Congress who suggested the Administration reallocate existing funds instead. The Administration continues to stress that the full request is still needed to fight both Zika and complete the Ebola response. With the announcement of the transfer of funds, the Administration is signaling that the risk of waiting for Congress to act on a supplemental funding is too great, and deploying additional funding to address Zika is essential in the short-term—before the summer weather leads to a broader spread of the mosquito-carried virus.Reallocating Ebola funding to address Zika carries consequences. While the Administration acknowledges that some Ebola funds remained unspent, much of this money has been allocated to implement the GHSA—a commitment to help at least 30 countries prevent, detect, and respond to emerging disease threats. GHSA has not received any direct appropriations, largely due to sentiment that remaining Ebola balances should cover the cost. Additionally, as the Ebola response remains unfinished—health systems in West Africa remain fragile and we have not yet developed approved Ebola vaccines or treatments—diverting funding before we have finished the job remains risky.Where is the money going? From where will it come? Vaccine researcher. Photo: NIAID, NIH Because the US Centers for Disease Control and Prevention (CDC) is focused on research and development (R&D) for Zika vaccines, treating those infected, and combating the mosquitoes that spread the virus, many expect the bulk of the $600 million transfer to be directed to CDC Zika efforts. The Washington Post reports that 75 percent of the transfer will go to CDC and the rest to foreign aid accounts. It remains uncertain from what accounts the Ebola transfers will come—and subsequently the impact on programs currently funded through the Ebola supplemental. It seems likely that much of the transfer may come from accounts at the US Agency for International Development and State Department, which as of December 31, 2015, had $400 million in programmed Ebola funds that will expire at the end of fiscal year 2016. Other accounts with remaining funds include: $1.031 billion at CDC for domestic, international, and global health security $363 million at Public Health and Social Services Emergency Fund, which houses the Biomedical Advanced Research and Development Authority $45 million at the US National Institutes of Health $14 million at the US Food and Drug Administration Funds in these accounts do not appear to have expiration dates. As we do not yet know for certain which accounts will fund the $600 million transfer, the impact of this decision on implementation of the GHSA is also uncertain.If funds are transferred from CDC accounts, GHSA efforts could be delayed or stalled. It also remains to be seen whether the Administration will receive additional funding to supplement the Zika response. While Congress has not acted on a request for a stand-alone supplemental funding, members have suggested they are open to providing additional funding in the future should the reallocation of existing funds prove insufficient to both addressing Zika and completing the Ebola response. The possibility remains that we could see additional funding for Zika as part of the regular appropriations process, which is likely to progress in the coming months. 

Amid the Zika outbreak and with new vector control approaches in the pipeline, there has been much talk about the feasibility and potential risks and benefits of eradicating mosquitos. National Institute of Allergy and Infectious Diseases (NIAID) Director Dr. Anthony Fauci advocated for mosquito elimination in a recent STAT News article, joking that their only known role in the natural ecosystem is feeding birds. However, Dr. Andrew Dobson, a professor of ecology and evolutionary biology at Princeton University, argues that such an approach would be “naïve and foolish,” noting that there are more than 3,000 mosquito species, hundreds that bite humans, but just three that are responsible for the vast majority of human disease transmission. Further, Dobson suggests that we can’t predict the consequences of mosquito eradication on the natural ecosystem, and that it could lead to the development of insecticide-resistant mosquitos. Meanwhile, NPR asked experts about the feasibility of eradicating even just one mosquito species and the resources required for it to be successful. First, global coordination mechanisms and high-level political will would be required, i.e., through the appointment of a United Nations mosquito czar. Next, financial resources are a must, with Pennsylvania State University Biologist and Entomologist Dr. Andrew Read estimating that US$250-500 million would be required to eliminate the Aedes aegypti mosquito—responsible for transmitting Zika, yellow fever, dengue, and chikungunya—a high pricetag but one that pales in comparison to the $1.5 billion pharmaceutical company Sanofi spent on developing a vaccine against just one of those diseases, dengue fever. With all the resources in place, the czar would then have to determine which vector control approach to take. As pathogens grow resistant to existing insecticides, both new insecticides and mutant mosquito interventions are under development. British biotech company Oxitec is currently testing its sterile-male mosquitos in Brazil. Oxitec’s mosquitos are released into the wild where they mate with female A. aegypti mosquitos, producing offspring that don’t live to adulthood and consequently can’t infect humans. The approach has resulted in an 82 percent decrease in the presence of A. aegypti larvae in the region in just nine months. Another intervention involves releasing mosquitos infected with Wolbachia bacteria, which then spreads among the mosquito population and can reduce the mosquitos’ ability to produce healthy offspring and to transmit viruses to humans. Finally, scientists are developing mosquitos using “gene-drive” technology, which involves releasing mosquitos genetically modified to be unable to lay eggs or transmit diseases. A team of scientists at the University of Texas Medical Branch (UTMB) have created a genetically modified mouse that is susceptible to Zika virus, making it the first animal model that can be used to test drugs and vaccines against the virus. The study, published in The American Journal of Tropical Medicine and Hygiene, provides further evidence that Zika is sexually transmitted and that it impacts the nervous system, as the viral load in mice was highest in the spleen, brain, and testes. The team, led by UTMB Virologist Dr. Shannan Rossi, developed the model in just three weeks, an impressive feat for a process that normally takes several months. UTMB scientists are also using the model to test an antiviral drug, developed for dengue fever, against Zika. The mouse model will be invaluable to scientists, particularly in light of the dearth of research on Zika. However, the mouse amnion—in which fetal development takes place—varies significantly from the human amnion, and thus, scientists are continuing to look for animal models that can shed light on the impact of Zika during pregnancy.