Encyclopedia of DNA Elements to be expanded for researchers

The US National Institutes of Health plans to expand its Encyclopedia of DNA Elements (ENCODE) Project, a genomics resource used by many scientists to study human health and disease. Funded by the National Human Genome Research Institute (NHGRI), part of NIH, the ENCODE Project is generating a catalogue of all the genes and regulatory elements -- the parts of the genome that control whether genes are active or not – in humans and select model organisms. With four years of additional support, NHGRI builds on a long-standing commitment to developing freely available genomics resources for use by the scientific community.

“ENCODE has created high-quality and easily accessible sets of data, tools and analyses that are being used extensively in studies to interpret genome sequences and to understand the consequence of genomic variation,” said Elise Feingold, Ph.D., a program director in the Division of Genome Sciences at NHGRI. “These awards provide the opportunity to strengthen this foundation by expanding the breadth and depth of the resource.” Since launching in 2003, ENCODE has funded a network of researchers to develop and apply methods for mapping candidate functional elements in the genome, and to analyse the enormous database of generated genomic information. The data and tools generated by ENCODE are organized by two groups: a data coordinating centre, which houses the data and provides access to the resource through an open-access portal, and a data analysis centre, which synthesizes the data into an encyclopaedia for use by the research community.

Pending the availability of funds, NHGRI plans to commit up to US$31.5 million in fiscal year 2017 for these awards. With this funding, ENCODE will expand the scope of these efforts to include characterization centres, which will study the biological role that candidate functional elements may play and develop methods to determine how they contribute to gene regulation in a variety of cell types and model systems. Additionally, the project will enhance the ENCODE catalogue by developing a way to incorporate data provided by the research community, and will use biological samples from research participants who have explicitly consented for unrestricted sharing of their genomic data.

At its core, ENCODE is about enabling the scientific community to make discoveries by using basic science approaches to understand genomes at the most fundamental level. Its catalogue of genomic information can be used for a variety of research projects – for example, generating hypotheses about what goes wrong in specific diseases or understanding the processes that determine how the same genome sequence is used in different parts of the body to make cells with specialized functions. More than 1,600 scientific publications by the research community have used ENCODE data or tools.

“We found that many of the people that are using the ENCODE resource are doing so for disease studies, and this attests to its translational value,” said Mike Pazin, Ph.D., a program director in NHGRI’s Division of Genome Sciences.

ENCODE Project
www.genome.gov/10005107/encode-project


Dengue vaccine phase 3 trial gets underway

Takeda Pharmaceutical Company has completed enrollment of 20,100 children and adolescents ages 4 through 16 in its global, pivotal Phase 3 Tetravalent Immunization against Dengue Efficacy Study (TIDES) trial, a double-blind, randomized and placebo-controlled study designed to evaluate the efficacy, safety and immunogenicity of its live-attenuated tetravalent dengue vaccine candidate (TAK-003).

The study is taking place in eight dengue- endemic countries in Latin America and Asia: Brazil, Colombia, Panama, Dominican Republic, Nicaragua, Philippines, Thailand and Sri Lanka. While dengue can affect people of all ages, it is a leading cause of serious illness among children in some countries in Latin America and Asia. The enrollment of children and adolescents between the ages of 4 and 16 years underscores the significant burden of dengue disease across the entire pediatric age range. Initial results of the TIDES trial are expected in 2018.

TIDES will build on previous studies which have assessed the tolerability, safety and immunogenicity of the vaccine against all four dengue serotypes in multiple age groups to determine whether the vaccine helps prevent symptomatic dengue.

“This enrollment milestone demonstrates our commitment to a thorough evaluation of the safety and efficacy of our vaccine candidates and, subject to licensure, ensuring that they are available to all populations at risk. It follows Takeda’s recent decision to invest more than 100 million euros to build a new plant for the manufacturing of TAK-003,” said Rajeev Venkayya, MD, President of the Global Vaccine Business Unit at Takeda.

TIDES Phase 3 trial is investigating thesafety and immunogenicity of two doses of TAK-003 administered three months apart.

The primary outcome measure is vaccine protection against virologicallyconfirmed dengue of any severity, caused by any of the four dengue virus serotypes, regardless of whether a subject has been previously exposed to dengue. Secondary endpoints include vaccine efficacy in preventing dengue induced by each dengue serotype, vaccine efficacy in preventing hospitalization due to dengue induced by any serotype, vaccine efficacy in preventing severe dengue induced by any serotype, frequency and severity of Adverse Events (AEs) or Serious Adverse Events (SAEs), and seropositivity rate and geometric mean titers (GMTs) of neutralizing antibodies in the immunogenicity subset.


WHO lists bacteria for which new antibiotics are urgently needed

WHO has published its first ever list of antibiotic-resistant “priority pathogens” – a catalogue of 12 families of bacteria that pose the greatest threat to human health.

The list was drawn up in a bid to guide and promote research and development (R&D) of new antibiotics, as part of WHO’s efforts to address growing global resistance to antimicrobial medicines.

The list highlights in particular the threat of gram-negative bacteria that are resistant to multiple antibiotics. These bacteria have built-in abilities to find new ways to resist treatment and can pass along genetic material that allows other bacteria to become drug-resistant as well.

“This list is a new tool to ensure R&D responds to urgent public health needs,” says Dr Marie-Paule Kieny, WHO’s Assistant Director-General for Health Systems and Innovation. “Antibiotic resistance is growing, and we are fast running out of treatment options. If we leave it to market forces alone, the new antibiotics we most urgently need are not going to be developed in time.”

The WHO list is divided into three categories according to the urgency of need for new antibiotics: critical, high and medium priority.

The most critical group of all includes multidrug resistant bacteria that pose a particular threat in hospitals, nursing homes, and among patients whose care requires devices such as ventilators and blood catheters. They include Acinetobacter, Pseudomonas and various Enterobacteriaceae (including Klebsiella, E. coli, Serratia, and Proteus). They can cause severe and often deadly infections such as bloodstream infections and pneumonia.

These bacteria have become resistant to a large number of antibiotics, including carbapenems and third generation cephalosporins – the best available antibiotics for treating multi-drug resistant bacteria. The second and third tiers in the list – the high and medium priority categories – contain other increasingly drug-resistant bacteria that cause more common diseases such as gonorrhoea and food poisoning caused by salmonella.

The list is intended to spur governments to put in place policies that incentivize basic science and advanced R&D by both publicly funded agencies and the private sector investing in new antibiotic discovery. It will provide guidance to new R&D initiatives such as the WHO/Drugs for Neglected Diseases initiative (DNDi) Global Antibiotic R&D Partnership that is engaging in not-for-profit development of new antibiotics.

Tuberculosis – whose resistance to traditional treatment has been growing in recent years – was not included in the list because it is targeted by other, dedicated programmes. Other bacteria that were not included, such as streptococcus A and B and chlamydia, have low levels of resistance to existing treatments and do not currently pose a significant public health threat.

While more R&D is vital, alone, it cannot solve the problem. To address resistance, there must also be better prevention of infections and appropriate use of existing antibiotics in humans and animals, as well as rational use of any new antibiotics that are developed in future.


WHO issues ethics guidance to protect rights of TB patients

New tuberculosis (TB) ethics guidance, launched by WHO, aims to help ensure that countries implementing the End TB Strategy adhere to sound ethical standards to protect the rights of all those affected.

TB, the world’s top infectious disease killer, claims 5000 lives each day. The heaviest burden is carried by communities which already face socio-economic challenges: migrants, refugees, prisoners, ethnic minorities, miners and others working and living in risk-prone settingsand marginalized women, children and older people.

“TB strikes some of the world’s poorest people hardest,” said Dr Margaret Chan, former WHO Director-General. “WHO is determined to overcome the stigma, discrimination, and other barriers that prevent so many of these people from obtaining the services they so badly need.”

Poverty, malnutrition, poor housing and sanitation, compounded by other risk factors such as HIV, tobacco, alcohol use and diabetes, can put people at heightened risk of TB and make it harder for them to access care. More than a third (4.3 million) of people with TB go undiagnosed or unreported, some receive no care at all and others access care of questionable quality.

The new WHO ethics guidance addresses contentious issues such as, the isolation of contagious patients, the rights of TB patients in prison, discriminatory policies against migrants affected by TB, among others. It emphasizes five key ethical obligations for governments, health workers, care providers, nongovernmental organizations, researchers and other stakeholders to:

• provide patients with the social support they need to fulfil their responsibilities

• refrain from isolating TB patients before exhausting all options to enable treatment adherence and only under very specific conditions

• enable “key populations” to access same standard of care offered to other citizens

• ensure all health workers operate in a safe environment

• rapidly share evidence from research to inform national and global TB policy updates.

Protecting human rights, ethics and equity are principles which underpin WHO’s End TB Strategy. But it is not easy to apply these principles on the ground. Patients, communities, health workers, policy makers and other stakeholders frequently face conflicts and ethical dilemmas. The current multidrug-resistant TB (MDR-TB) crisis and the health security threat it poses accentuate the situation even further. “Only when evidence-based, effective interventions are informed by a sound ethical framework, and respect for human rights, will we be successful in reaching our ambitious goals of ending the TB epidemic and achieving universal health coverage. The SDG aspiration of leaving no one behind is centred on this,” said Dr Mario Raviglione, Director, WHO Global TB Programme.

“The guidance we have released aims to identify the ethical predicaments faced in TB care delivery, and highlights key actions that can be taken to address them,” he added.

Ethics guidance for the implementation of the End TB Strategy www.who.int/tb/publications/2017/ethics-guidance


Global Patient Safety Challenge on Medication Safety launched

WHO has launched a global initiative to reduce severe, avoidable medication-associated harm in all countries by 50% over the next 5 years.

The Global Patient Safety Challenge on Medication Safety aims to address the weaknesses in health systems that lead to medication errors and the severe harm that results. It lays out ways to improve the way medicines are prescribed, distributed and consumed, and increase awareness among patients about the risks associated with the improper use of medication.

Medication errors cause at least one death every day and injure approximately 1.3 million people annually in the United States alone. While low- and middleincome countries are estimated to have similar rates of medication-related adverse events to high-income countries, the impact is about twice as much in terms of the number of years of healthy life lost. Many countries lack good data, which will be gathered as part of the initiative.

Globally, the cost associated with medication errors has been estimated at US$42 billion annually or almost 1% of total global health expenditure.

Both health workers and patients can make mistakes that result in severe harm, such as ordering, prescribing, dispensing, preparing, administering or consuming the wrong medication or the wrong dose at the wrong time. But all medication errors are potentially avoidable. Preventing errors and the harm that results requires putting systems and procedures in place to ensure the right patient receives the right medication at the right dose via the right route at the right time.

Medication errors can be caused by health worker fatigue, overcrowding, staff shortages, poor training and the wrong information being given to patients, among other reasons. Any one of these, or a combination, can affect the prescribing, dispensing, consumption, and monitoring of medications, which can result in severe harm, disability and even death.

Most harm arises from systems failures in the way care is organized and coordinated, especially when multiple health providers are involved in a patient’s care. An organizational culture that routinely implements best practices and that avoids blame when mistakes are made is the best environment for safe care.

The Challenge calls on countries to take early priority action to address these key factors: including medicines with a high risk of harm if used improperly; patients who take multiple medications for different diseases and conditions; and patients going through transitions of care, in order to reduce medication errors and harm to patients.

The actions planned in the Challenge will be focused on four areas: patients and the public; health care professionals; medicines as products; and systems and practices of medication. The Challenge aims to makeimprovements in each stage of the medication use process including prescribing, dispensing, administering, monitoring and use. WHO aims to provide guidance and develop strategies, plans and tools to ensure that the medication process has the safety of patients at its core, in all health care facilities.

This challenge is WHO’s third global patient safety challenge, following the Clean Care is Safe Care challenge on hand hygiene in 2005 and the Safe Surgery Saves Lives challenge in 2008.


US NIAID funds international malaria research centres

The US National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, announced approximately US$9 million in first-year funding, subject to availability, for seven malaria research centres around the world. The 7-year awards continue NIAID’s 2010 program that created the International Centers of Excellence for Malaria Research (ICEMRs) in regions where malaria is endemic. The awards fund three new and four existing centres that work in 14 countries in Africa, Asia and Latin America.

“NIAID-supported ICEMRs have made significant contributions to malaria research since their creation in July 2010,” said NIAID Director Anthony S. Fauci, M.D. “We look forward to their continued multidisciplinary efforts to further our understanding of the complex interactions between human hosts, mosquito vectors and the Plasmodium parasites that cause malaria, so that we may work toward controlling, eliminating and eventually eradicating this global scourge.”

Despite significant progress in reducing malaria incidence and mortality, the World Health Organization estimates that 212 million new cases of malaria and 429,000 malaria deaths occurred in 2015, mostly in Africa. Although numerous vaccine candidates to prevent malaria are in development, none have been approved for widespread use. Effective malaria drugs are available, but some have severe side effects, may be difficult to procure in remote regions, and are losing their effectiveness in some places as malaria- causing parasites have developed resistance. Mosquito control, which relies largely on bed nets and insecticides, is still a front-line defence in regions where malaria is endemic, but changes in mosquito behaviour and insecticide resistance are increasing concerns.

“The 2017 awards under the ICEMR program will enable scientists to continue vital malaria research, which often straddles disciplines to address the most pressing problems and practicalities of fighting malaria,” said Lee Hall, M.D., Ph.D., Chief of NIAID’s Parasitology and International Programs Branch.

Under the previous awards, ICEMR researchers found evidence that some current rapid diagnostic tests are failing to detect malaria in some regions because malaria parasites do not always express the antigen the test is designed to detect. ICEMR research also has confirmed a significant shift in the behaviour of some malaria-carrying mosquitoes, perhaps in response to malaria control measures. Malaria is typically transmitted by Anopheles mosquitoes biting indoors late at night, but more mosquitoes now appear to be biting outdoors and earlier in the evening, when people are not sleeping under protective bed nets.

The recipients of the ICEMR awards announced today are as follows:

  • Amazonian Center of Excellence in Malaria Research. Lead Institution: University of California, San Diego.
  • Multidisciplinary Research for Malaria Control and Prevention in West Africa*. Lead Institution: University of Sciences, Techniques & Technologies of Bamako, Bamako, Mali.
  • Malaria Transmission and the Impact of Control Efforts in Southern and Central Africa. Lead Institution: Johns Hopkins Bloomberg School of Public Health, Baltimore.
  • Program for Resistance, Immunology, Surveillance & Modeling of Malaria in Uganda (PRISM). Lead Institution: University of California, San Francisco.
  • Environmental Modifications in sub- Saharan Africa: Changing Epidemiology, Transmission and Pathogenesis of Plasmodium falciparum and P. vivax Malaria*. Lead Institution: University of California, Irvine.
  • Southeast Asia Malaria Research Center. Lead Institution: Pennsylvania State University, University Park.
  • Myanmar Regional Center of Excellence for Malaria Research*. Lead Institution: University of Maryland School of Medicine, Baltimore.

*This is a new ICEMR institution.

 

 

Date of upload: 13th May 2017

                                  
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