Breakthroughs Blog: Diagnostics

2016 was a year that ushered in significant shifts in the global health landscape. We witnessed the waning of the Ebola epidemic and the waxing of the Zika outbreak; important leadership changes among the biggest institutional players in global health; and the development and introduction of new innovations that could turn the tide against leading infectious disease killers. As the year comes to an end, GHTC is reflecting on the top stories in global health innovation that made news in 2016. Here are seven of those top moments: 1. Scientists mobilize against Zika A vial of the National Institute of Allergy and Infectious Diseases (NIAID) Zika Virus Investigational DNA Vaccine (Photo: NIAID).Once considered an obscure virus responsible for a mild illness, Zika took the world by storm in 2016. As the virus gained a foothold in more than 60 countries, its association with devastating birth defects and neurological conditions was firmly established. Prior to Zika’s emergence in the Americas, only 25 research papers had been published on the virus. As the epidemic grew, scientists around the world joined the fight against Zika, often sharing their data and research in real time to speed progress. Thanks to the efforts of these researchers, over the past year our scientific understanding of Zika has grown exponentially, and we have advanced a robust pipeline of new tools to prevent, detect, and treat Zika. Today, there are more than 35 Zika vaccine candidates under development; 13 Zika diagnostics have been authorized for use by the US Food and Drug Administration; and researchers are screening novel compounds and evaluating existing drugs to advance treatments for the disease. 2. The world commits to the fight against antimicrobial resistance United Nations General Assembly (Photo: GHTC/Matthew Robinson). 2016 marked the year the world finally got serious about tackling antimicrobial resistance. On the heels of several major analyses examining the potentially devastating health and economic impact of antimicrobial resistance, the United Nations (UN) General Assembly convened global leaders for a high-level summit on antimicrobial resistance—the fourth time such a meeting has been held on a health-related topic during the UN’s 71-year history. At the close of the summit, UN member states unanimously endorsed and adopted a political declaration committing to developing action plans and policies; mobilizing resources; and supporting public awareness, surveillance, and R&D efforts to combat antimicrobial resistance. It is our hope that 2017 will mark the year political commitment translates to concrete action to advance the development of new antibiotics. 3. New strategies deployed to stymie mosquito-borne diseases Mosquito-borne diseases remain an age-old scourge, but 2016 saw the advancement of several novel strategies to combat these tiny foes. Efforts to combat mosquito-borne diseases with the transmission blocking–bacteria Wolbachia took an important leap forward this year. Past studies have shown that when the Wolbachia bacteria is introduced to Aedes aegypti mosquitos—which carry viruses like Zika and yellow fever—it prevents the viruses from replicating and blocks further transmission. Because the bacteria can be passed from one generation of mosquitoes to the next, the bacteria offers hope for eliminating a virus’s presence within a local mosquito population. After several years of conducting small-scale tests of this method, the Eliminate Dengue Program announced in 2016 it would begin conducting two large-scale trials in South America to determine whether this approach is effective in halting the spread of mosquito-borne diseases in large urban settings. This year the biotech company Oxitec also advanced efforts to test the use of genetically modified mosquitoes to reduce mosquito populations and disease transmission. The company has engineered mosquitoes that mate with A. aegypti mosquitoes, producing offspring that are unable to mature to adulthood. Early last year, Oxitec introduced the mosquitoes into the Brazilian city of Piracicaba, resulting in an 82 percent decrease in the population of A. aegypti mosquitoes in just nine months. Now, Oxitec has expanded the trial to a larger geographical area and is also initiating trials in the Florida Keys and the Cayman Islands. 4. World’s first kid-friendly TB medicine launches Children who receive tuberculosis (TB) medicines require a different dose than adults, yet until this year, there were no TB medicines designed specifically for children, so parents were forced to split or crush adult pills in an attempt to administer the right dose to their child. This year, that all changed with the launch of the world’s first kid-friendly TB medication. Developed by TB Alliance, the medicine is designed with the unique needs of children in mind: It is fruit-flavored, dissolvable in water, easy to administer, and appropriately-dosed. Already, more than 30 countries have adopted the new medicines, and enough orders have been placed to treat half of childhood TB cases worldwide. 5. Unique HIV prevention option for women reaches important development milestone Image captionMonthly vaginal dapivirine ring helps protect women against HIV (Photo: International Partnership for Microbicides). Women may soon have a powerful new tool at their disposal to prevent HIV infection. Earlier this year, the International Partnership for Microbicides (IPM) announced the results of two large phase 3 clinical trials demonstrating that a monthly vaginal ring containing the antiretroviral drug dapivirine can help protect women from HIV. While initial results indicated that the dapivirine ring reduced HIV risk by approximately 30 percent, further analysis revealed that the ring reduced infection rates by 75 percent in women who used the ring consistently. Now, IPM is seeking regulatory approval for the dapivirine ring and is conducting open-label studies, enabling trial participants to continue using the ring as IPM collects additional data. The dapivirine ring is the only long-acting, female-initiated HIV prevention tool to have proven successful in phase 3 clinical trials. Young women in sub-Saharan Africa are more than twice as likely to be infected with HIV than their male counterparts, and thus female-centered prevention tools are needed stem the epidemic. 6. Roll out begins of world’s first malaria vaccine candidate After decades of development and testing, the world’s first malaria vaccine candidate will soon be introduced in several communities in sub-Saharan Africa. The vaccine—RTS,S—was developed by PATH and GlaxoSmithKline and received a positive opinion from the European Medicines Agency last year following completion of phase 3 clinical trials. In November, the World Health Organization (WHO) announced it would pilot and evaluate the vaccine in real-life settings, thanks to funding from The Global Fund; UNITAID; and Gavi, the Vaccine Alliance. Pending results of these pilot tests, WHO will determine whether to deploy the vaccine on a wider scale. 7. New global health technologies advance through the pipeline PATH launches an easy-to-use, rapid diagnostic for onchocerciasis (Photo: PATH/Dunia Faulx) Over the past year, several other promising new health innovations have moved through the development pipeline and one step closer to reaching the hands of patients: Two important health tools—a novel, affordable oral cholera vaccine developed by the International Vaccine Institute, and the Woman’s Condom developed by PATH and partners—received WHO prequalification this year, paving the way for their procurement by UN agencies and other international procurement organizations. Two new rapid diagnostic tests for the neglected tropical diseases onchocerciasis (river blindness) and lymphatic filariasis were launched this year. Developed by PATH, these tests provide results in just 30 minutes and can be stored at a wide range of temperatures. Development has begun for an affordable therapy for hepatitis C. In 2013, the world’s first cures for hepatitis C hit the US market, however, treatment remains out of reach for many patients due to the high price tag. This year, the Drugs for Neglected Diseases initiative announced it would begin testing an alternative therapy in phase 2 and 3 clinical trials, with a guarantee from the manufacturer that, if successful, the entire regimen will be sold for no more than US$294.  As 2016 draws to a close and 2017 begins, it is time for the global health community to redouble our efforts to make sure this vital progress in global health innovation continues to ensure that people around the world will have access to lifesaving and life-improving health technologies.

It’s that time of year when Americans join together with family and friends and give thanks for the many things in life for which they are most grateful. In the spirit of the Thanksgiving holiday, GHTC asked our members and staff to share what they are most thankful for in global health. Here’s what they had to say: “I am thankful for all patients who take part in clinical trials so that the world will have more effective regimens to end TB, in all its forms.” Willo Brock, Senior Vice President of External Affairs, TB Alliance “I’m thankful there is increasing global interest in the development and production of vaccines for diseases of poverty, like hookworm, schistosomiasis, and Chagas.” Tara Bracken, Communications Associate, Sabin Vaccine Institute “I am thankful that 2016 was a turning point for women’s HIV prevention research—one that brought us hope for one day soon expanding women’s options with a long-acting vaginal ring. I am also grateful for the amazing partners who believe women’s health and empowerment matter!” Zeda Rosenberg, Founder and CEO, International Partnership for Microbicides “I’m thankful for the new generation of emerging R&D leaders who are both generating new knowledge and achieving global health impact.” Dr. Timothy Mastro, Chief Science Officer, FHI 360 “I’m thankful for sustained US government funding to fight emerging epidemics, like Ebola and Zika, through R&D and scientific advancement.” Lindsay Litwin, Jhpiego Innovations “I’m thankful that elimination of sleeping sickness is now a real possibility thanks to new tests being strategically implemented alongside new vector control technologies and improved treatment regimens.” Dr. Joseph Ndung’u, Head of Neglected Tropical Diseases Programme, FIND “I’m thankful that the six antimalarials MMV and partners have brought forward are saving young lives today!” Andrea Lucard, Executive Vice President of External Relations, Medicines for Malaria Venture “I’m thankful for research that has shown promise for an effective six-month regimen to cure XDR-TB [extensively drug-resistant TB].” Rabita Aziz, Policy Research Coordinator, ISDA Global Health “I’m thankful for the inspirational dedication and continued participation of all HIV vaccine clinical trial volunteers. Without you, the important work of finding a safe and effective HIV vaccine would not be possible.” Dr. Fran Priddy, Chief Medical Officer, International AIDS Vaccine Initiative “I’m thankful for the over 200 members of Congress who have co-sponsored the Reach Act to accelerate efforts to end preventable deaths of mothers and children around the world.” Brandon Ball, Policy and Advocacy Officer, PATH "I'm thankful for low-cost interventions like chlorhexidine gel for umbilical cord care being made more accessible to Sub-Saharan Africa to reduce newborn mortality." Assumpta Nantume, Communications Associate/Global Health Corps Fellow, Global Health Council “I'm thankful a new generation of Middle Eastern scientists are advancing the development, production, and characterization of new vaccines to help endemic countries better respond to the threat of infectious diseases like MERS, schistosomiasis, and leishmaniasis.” Chris Bennett, Senior Program Officer, Sabin Vaccine Institute “I’m thankful for pioneering donors such as UNITAID for funding development of new hepatitis C tests for countries where fewer than 1 percent of people living with hepatitis C have been diagnosed.” Catharina Boehme, Chief Executive Officer, FIND “I’m thankful for scientists and researchers who devote their lives to important global infectious disease work to help people around the world and to protect Americans here at home and the funding the US government provides for such important work.” Karen Goraleski, Executive Director, American Society for Tropical Medicine and Hygiene “I’m thankful for the tremendous progress we’ve made in advancing child and maternal survival and excited for the prospect of saving the lives of more than 6 million mothers and children by 2030 if we work together to advance and scale-up 11 promising innovations.” Heather Ignatius, Multilateral, US, and Europe Policy & Advocacy Team Lead, PATH “I’m thankful for researchers across the globe whose efforts have, with unprecedented speed, deepened our scientific understanding of and advanced new tools to prevent, detect, and treat Zika.” Kat Kelley, Senior Program Assistant, GHTC “I'm thankful so many good dengue vaccine candidates are in development that could help curb the growing global dengue epidemic.” Tara Bracken, Communications Associate, Sabin Vaccine Institute "I'm thankful for increased awareness on global antibiotic resistance and WHO's new evidence-based Infection Prevention and Control Guidelines." Danielle Heiberg, Advocacy Manager, Global Health Council “I'm thankful for the lives of mothers and babies that have been saved, sustained, and supported by midwives across the globe.” Shannon Egan, Jhpiego Innovations “I’m thankful that malaria rapid tests have contributed to better malaria control, which in turn has helped fuel a massive decline in childhood mortality over the past decade—and that partners around the world are working together to find innovative new solutions for identifying non-malarial causes of fever. Diagnosis matters!” Dr. Iveth J. González, Head of Malaria and Acute Febrile Syndrome programme, FIND “I’m thankful for the support of MMV’s committed donors and partners that make our work to develop new antimalarials for vulnerable populations possible.” Andrea Lucard, Executive Vice President of External Relations, Medicines for Malaria Venture “I’m thankful to be a part of the #StartStayAIDSFree initiative which aims to end AIDS in children by 2020.” Catherine Connor, Senior Director of Public Policy and Advocacy, Elizabeth Glaser Pediatric AIDS Foundation “I’m thankful that members of both major US political parties have continued to demonstrate strong, bipartisan support for global health research and development and US efforts to save lives around the world.” Marissa Chmiola, Communications Officer, GHTC

Researchers examine onchocerciasis (river blindness) diagnostic tests. PATH/Patrick McKernWithout the right diagnostics, we can’t effectively treat diseases. It’s an obvious statement. But in many low- and middle-income countries, doctors and health care workers don’t have access to the diagnostic tools they need, often because existing tests are too costly and not appropriate for low-resource settings or tests don’t exist at all. Without the right tests, doctors end up relying on patient symptoms, which can be remarkably similar across different diseases. The result can be devastating: A wrong diagnosis can lead to the wrong treatment or a failure to recognize the presence of disease with pandemic potential. This problem is a common one: in half of African countries, more than 80 percent of those treated for malaria receive medicine without confirmation of a diagnostics, and during the 2014–2015 Ebola outbreak, efforts to contain the outbreak were hampered by a lack of rapid, point-of-care tests that could be deployed easily in the field.In a recent New England Journal of Medicine article, a group of scientists and doctors suggested an innovative idea to improve global access to critically-needed diagnostic tools: create a list.More specifically, they’re calling for the creation of an essential diagnostics list to complement the World Health Organization’s (WHO) Model List of Essential Medicines (EML). The EML provides guidance to countries on what drugs, therapies, and treatments should be made available to citizens to meet basic public health needs. Likewise, an essential diagnostics list would provide guidance on the vital diagnostics tests that should be available in each country, depending on its disease burden. In this way, the two lists would support and complement each other, with the diagnostics list identifying the tests needed to enable appropriate use of medicines on the EML.The transformative potential of an essential diagnostics listThe authors of the article have detailed the many ways an essential diagnostics list could be a transformative force for improving diagnostic capacity and access. By setting global guidance on the diagnostics tests recommended to countries to address basic health needs, an essential diagnostics list could provide a forceful policy argument for governments to invest in making existing diagnostics more broadly available. A list could also encourage governments to make further improvements to health systems to support diagnostic use, including laboratory training programs and strengthening health infrastructure and supply chains.But what GHTC is most excited about is one of the lesser-discussed aspects of an essential diagnostics list: its potential to catalyze research and development (R&D) of new diagnostic tools. A patient gets tested for malaria. PATH/Gena Morgan Diagnostic R&D is a significantly underfunded area of research, accounting for less than 5 percent of global funding of neglected disease R&D. The result is a lack of diagnostic tools targeting the specific health needs of low- and middle-income countries, such as easy-to-use platform technologies or rapid, point-of-care tests that can be used in remote, rural clinics.By detailing which diagnostics are necessary to support health interventions on the EML, an essential diagnostics list would readily expose health areas where we today lack appropriate and effective tools. In this way, the list could signal to product developers, industry, and donors where funding and attention is needed to facilitate diagnostic R&D.The impact of improved diagnostic access and capacity would be considerable: better care and treatment for patients, reduction in the inappropriate use of medicines which is contributing to drug resistance, and improved ability to detect emerging diseases like Zika and Ebola early before they become epidemics.Joining the call for an essential diagnostics listOn Wednesday, GHTC sent a letter, signed by 11 of our member organizations, to WHO’s assistant director-general for Health Systems and Innovation calling for WHO to spearhead the creation of an essential diagnostics list. Given WHO’s experience in administering the EML and its ongoing work in providing guidance on diagnostic testing and laboratory accreditation; we believe the organization is uniquely positioned to lead on the development and implementation of this list. But making this initiative a reality will require the support of civil society and member states, as well as additional funding to stand-up the program at WHO.It is clear that treatment can be improved with essential diagnostics—ones we have today and others yet to be developed. We urge WHO and its member states to heed this call to establish an essential diagnostics list. It’s a smart, cost-effective idea that could advance diagnostic R&D and access.Update: On November 18, Dr. Marie-Paule Kieny, WHO Assistant Director-General for Health Systems and Innovation, replied to GHTC's letter indicating that WHO is pursuing analysis of the idea and outlining next steps. GHTC will continue to monitor progress and engage with WHO in support of this initiative.

The US National Institutes of Health (NIH) announced the Antimicrobial Resistance Diagnostic Challenge last week, a competition which will award US$20 million for the development of rapid, point-of-care diagnostics to combat antimicrobial resistance. The competition will be funded by NIH's National Institute of Allergy and Infectious Diseases and the US Department of Health and Human Services’ Biomedical Advanced Research and Development Authority, while the US Centers for Disease Control and Prevention and the US Food and Drug Administration will provide scientific and regulatory expertise. Eligible diagnostics are those that either test for drug-resistant bacteria or differentiate between viral and bacterial infections, critical tools to reduce ineffective and unnecessary antibiotic prescriptions. The recently launched Coalition for Epidemic Preparedness Innovations (CEPI) will fund early stage human clinical trials and stockpile vaccine candidates for the viruses most likely to cause the next major epidemic. CEPI will collaborate with product developers and the World Health Organization (WHO) to facilitate regulatory review of vaccine candidates and to ensure that large scale clinical trials can be rapidly rolled out in the case of an outbreak. Eligible vaccine candidates will target viruses identified by the WHO as the greatest threats, including Crimean Congo hemorrhagic fever, Ebola and Marburg, Lassa fever, Rift Valley fever, Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS), and Nipah virus. The coalition was formed by the governments of India and Norway, philanthropic organizations the Wellcome Trust and the Bill & Melinda Gates Foundation, and the World Economic Forum and will be housed at the Norwegian Institute for Public Health in Oslo. The International Vaccine Institute (IVI) is partnering with Xiamen Innovax Biotech Co., Ltd. (Innovax) to expand access to the world’s first and only vaccine against Hepatitis E—a viral disease that causes 20 million infections and results in 70,000 deaths and 3,000 stillbirths each year. The vaccine, Hecolin®, was developed by Innovax and is only licensed for use in China. The Gates Foundation will support an assessment of the vaccine to determine its eligibility for WHO prequalification—a process that evaluates the safety, efficacy, and quality of a specific health tool produced by a specific manufacturer and that enables the product to be purchased by United Nations agencies. Hecolin® offered complete protection against hepatitis E in a phase 3 clinical trial with more than 100,000 participants. Pharmaceutical company Takeda has initiated a phase 3 clinical trial of its vaccine candidate against dengue fever, a mosquito-borne infection caused by four closely related viruses. Last year, pharmaceutical company Sanofi launched the world’s first dengue vaccine, however, new research suggests that the vaccine could actually increase the severity of infections in children who have never been exposed to dengue. This is due to antibody-dependent enhancement, in which protective antibodies against a virus (in this case, one strain of dengue virus) can actually help related viruses (the other three strains of dengue virus) attack human cells. Consequently, the antibodies produced by children receiving the vaccine could actually exacerbate the symptoms of future infections. In phase 1 and 2 trials, Takeda’s vaccine candidate appeared to be safe and resulted in the production of antibodies against all four strains of the virus. For its phase 3 trial, Takeda plans to enroll 20,000 children in dengue-endemic nations in Latin America and Asia. The trial will evaluate safety and efficacy against all four strains of dengue and in children with and without prior exposure to the virus.