Global challenges and opportunities for tackling antimicrobial resistance

This post was written by Sophie Allcock andoriginally posted on the Global Health, Epidemiology and Genomics blog – view more at: http://gheg-journal.co.uk/blog/

Antimicrobial resistance (AMR) is a global public health concern. In 2014, an estimated 700,000 deaths were attributed to AMR globally and it is predicted that by 2050 this number could reach 10 million.[1] Antibiotics have been the cornerstone of many medical interventions, for example surgical interventions, transplants and the treatment of common bacterial infections, for decades. Without effective antibiotics, many medical practices that we now consider to be routine will be jeopardised.

Although there is much global attention to AMR, there is a need to better understand the burden, distribution and determinants of AMR at the population level. Antimicrobial use, appropriate or inappropriate, is a driver of AMR yet there is a lack of specific advice as to which interventions are likely to have the greatest impact on reducing the emergence and spread of AMR in both hospital and community settings.

In our paper “Antimicrobial resistance in human populations: challenges and opportunities”, we argue for the integration of a range of epidemiological approaches, which could help to improve our understanding of the population level factors that may influence the development and spread of AMR. This is important for informing interventions to reducing excess use of antimicrobials, whilst also ensuring that those in need of these treatments have access to them.

One such approach is to use routine clinical data and electronic health records (EHRs) in combination with pathogen surveillance, using techniques such as whole-genome sequencing. This could help to improve our understanding of drug resistance, how it emerges and how it spreads. EHRs could also provide an insight into prescribing practices in general practices and hospitals, and how this could be related to the emergence of drug-resistant infections. Using prospective (or longitudinal) study designs, researchers could explore the real-time development of resistant strains in a given population as well as the factors that may drive resistance.

Other preventative strategies to reduce the burden of AMR include basic hygiene and sanitation practices, waste management and safe food preparation. However, in some low- and middle-income countries (LMICs), conducting these basic practices can be challenging due to human resource constrains and weaker civil and health infrastructures. Furthermore, it is often the case in these countries that more people suffer due to a lack of access to drugs than drug resistance itself.

The suggested research initiatives may help to better understand the burden, distribution and determinants of AMR. These approaches should be combined with improved preventative measures, including vaccinations and good hygiene and sanitation practices to reduce the need for therapy in the first instance, and strategies to reduce excess use of antimicrobials to slow the development of resistance. Furthermore, although AMR is a global problem, we need to consider that the issue differs by county and setting, therefore so must the approach taken to tackle AMR.

Reference:
1. O’Niell J., Tackling Drug-Resistant Infections Globally: Final Report and Recommendations, in The review on antimicrobial resistance. 2016, HM Government and the Wellcome Trust: London.

The paper “Antimicrobial resistance in human populations: challenges and opportunities” by S. Allcock, E. H. Young, M. Holmes, D. Gurdasani, G. Dougan, M. S. Sandhu, L. Solomon and M. E. Török has been published Open Access in Global Health, Epidemiology and Genomics and is available here.

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Free Content about the Zika Virus Now Available

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Just 8 days after the public health emergency was declared, this content regarding the Zika virus has been written, reviewed, edited, and released as a freely available resource.

On February 1st, the World Health Organization declared a Public Health Emergency of International Concern related to clusters of microephaly cases in some areas affected by the Zika virus. Like the Ebola virus, there had been very little funding and research on Zika until the recent emergency and associated media and scientific attention – there is therefore a dearth of information and there is neither a vaccine nor prophylactic pharmacotherapy available to prevent Zika virus infection.

In response to concern over the effects of Zika virus infection in pregnant women, the medical publishing team at Cambridge University Press commissioned a brief summary of current evidence and recommendations. Just 8 days after the public health emergency was declared, this content has been written, reviewed, edited and released as a freely available resource. The content has been provided by Professor Bernard Gonik, Fann S. Srere Chair of Perinatal Medicine, Wayne State University School of Medicine.

Released in advance as a freely accessible public resource, this content is part of High-Risk Pregnancy: Management Options – a forthcoming updateable online product from Cambridge University Press. Like all of the content in High-Risk Pregnancy: Management Options, the Zika section will be regularly updated as new information arises.

Read about the Zika Virus Here

 

Announcing the publication of the first papers in GHEG

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We are delighted to announce the publication of the first papers in Global Health, Epidemiology and Genomics. As GHEG is fully Open Access, these papers, and all papers published in the future, are freely accessible online. Here we provide a brief summary of our first three publications.

 A forum for global population health, technological advances and implementation science
 Manjinder Sandhu

A welcome editorial by our Editor in Chief, marking the launch of Global Health, Epidemiology and Genomics. Dr Sandhu highlights the strengths of the broad interdisciplinary scope of the journal and its international editorial board and invites the global health community to engage and contribute to the journal so that it becomes a valuable, practical and informative resource.
Read the full article here

 

favicon Study Profile: The Durban Diabetes Study (DDS): a platform for chronic disease research
 Thomas Hird et al.

A study profile of The Durban Diabetes Study (DDS), an on-going population-based cross-sectional survey of an urban black population in Durban, South Africa. The DDS was established to investigate a broad range of lifestyle, medical and genetic factors and their association with diabetes. It provides a rich platform for investigating the distribution, interrelation and aetiology of other chronic diseases and their risk factors, which can be utilised for other research studies.
Read the full article here

 

Favicon long Capitalizing on Natural Experiments in Low- to Middle- Income Countries to Explore Epigenetic Contributions to Disease Risk in Migrant Populations
 J. Jaime Miranda et al.

 

A commentary on the value of epigenetics as a tool for understanding differential disease risk in migrant populations. The authors highlight the merit of exploring migrant chronic disease risk in low- to middle-income countries, particularly in the context of rural-to-urban migration, with increasing urbanisation in this setting.
Read the full article here
More articles will be published in the coming weeks, and you can be notified when new articles are published by signing up to content alerts here. Here’s a preview of what’s coming soon:

  • H3Africa Multi-Centre Study of the Prevalence and Environmental and Genetic Determinants of Type 2 Diabetes in Sub-Saharan Africa: Study Protocol
    Kenneth Ekoru et al.
  • Regulatory Developments in the Conduct of Clinical Trials in India
    Dhvani Mehta and Ranjit Roy Chaudhury

GHEG accepts original research articles, brief reports, structured reviews and commentaries as well as protocols, research resources and analysis. We are waiving the Article Processing Charge for all articles submitted to GHEG before the end of 2016. We invite contributions from a range of disciplines:
Epidemiology, Clinical trials, Genetics, Observational studies, Qualitative studies, Anthropological studies, Social science, Community intervention, Health systems, Health services, Population genetics, Population history.
For further information on the journal and how to submit please visit our website. Or if you wish to submit your manuscript directly please visit: http://mc.manuscriptcentral.com/gheg.

Only One Flu Shot? Maybe!

Can you imagine not having to get a flu shot every season? Apparently two independent teams of doctors have been imagining the same thing.

The two independent research groups have released findings that this could be a reality someday.

It has been notoriously difficult to formulate a vaccine against all forms of influenza for a number of reasons. One thing that makes the virus so difficult is that influenza is a shape shifter that can, and does, mutate and change quickly and repeatedly. This means that even if a person develops immunity through an earlier year’s flu shot, he might not be immune to the latest strain of the virus.

A large portion of the human immune response to the flu is directed against a portion of the protein hemagglutinin called the hemagglutinin head. In the last twenty years scientists discovered that some people were able to fight a large swath of flus because their immune systems could develop antibodies that targeted the hemagglutinin stem. Even so though, the human immune system still often cannot keep up with the rapidly mutating stem. This could be partially due to the fact that the stem is hidden while the head is exposed.

Knowing this, the two independent research teams took two different approaches to almost identical notions. With idea to help the body create more stem-specific antibodies in order to help battle more types of influenza, each team decided to focus exclusively on the hemagglutinin stem. Their idea was to create stem-only antigens to incorporate into vaccines, effectively ignoring the hemagglutinin head.

This proved a very difficult task, “Flu is a very large virus with lots of parts. It’s very hard to build a small piece without screwing things up,”  Andrew Ward told the Los Angeles Times a structural biologist at Scripps Research Institute. In order to create a stable molecule and not disrupt the response they wished-for for the antibodies, they could not have a single atom out of place.

Incredibly, the two teams were able to create stable molecules and were able to use them to create vaccines which they tested on mice and monkeys and mice and ferrets respectively. They were both able to elicit certain protection in varying degrees.

This, by no means, means that a universal flu vaccine will be available in the short term. However, it paves the way for a type of booster shot that could be available at some point in the future and more protection against the flu than current shots, which only can protect against 3 or 4 strains, says Ward.

Psychiatric Genetic Revolution – is calcium the key?

DNA Rendering. Photo: ynse. used under CretaiveCommons

DNA Rendering. Photo: ynse. used under CreativeCommons

Dr. Berrettini and I published Principles of Psychiatric Genetics in late 2012. Since then, there have been several interesting developments in Psychiatric Genetics worth calling your attention to. The first is a set of articles from the Cross-Disorder Group of the Psychiatric Genomics Consortium (PGC). The PGC has revolutionized the field of psychiatric genetics in the last decade by bringing together investigators from around the world to pool their carefully collected clinical samples in order to provide the numbers for powerful analyses of common gene variants in major psychiatric disorders such as schizophrenia and bipolar disorder. Whereas the original genome-wide association studies in psychiatry included ~1000 cases and 1000 controls, we are now able to amass collections of 25,000 cases with schizophrenia and 37,000 controls because investigators have come together under the PGC umbrella. This has provided the power to detect more than 100 common single gene variants associated with schizophrenia.

The particular article I wanted to feature was one from the Cross-Disorder Group in that consortium (Cross-Disorder Group of the PGC, Lancet, 2013). Samples were combined from persons with schizophrenia, bipolar disorder, depression, attention-deficit hyperactivity disorder, and autism. There were four single gene variants that were identified from the group of disorders considered together. The fascinating aspect of this was that two of the four were genes controlling calcium channels in the brain. The investigators were also able to test an entire group of calcium-channel related genes (72 genes in all) and demonstrate that variations in this set of gene markers was associated with vulnerability to these conditions, especially to schizophrenia and bipolar disorder. This is a new finding in psychiatry, and it is potentially very relevant to clinical management of these conditions. Calcium channel abnormalities have been described in these disorders, but this hypothesis was not central to a consideration of the neurobiology of these disorders. Over the past three decades, much more energy has been spent on theories involving neurotransmitters such as serotonin, dopamine, and norepinephrine. However, it may be that calcium channel signaling problems are causal to neurotransmitter variation. Calcium flow into the cell is necessary for cell excitation and signaling. Many of the critical second messenger systems in the cell (which carry a signal within the cell after a neurotransmitter hits its target receptor) are dependent on calcium.

Calcium channel inhibitors are available, and have been used to treat cardiovascular conditions for several decades (e.g., verapamil, nifedipine, nimodipine) . They have also been used to treat psychiatric conditions, with some success, but not consistent success. It may be that these agents must be targeted to specific individuals who demonstrate calcium channel gene abnormalities. Or it may be that newly designed drugs with more subtle effects on calcium activity are needed. In any case, this seems like an important clue with ramifications for our understanding of the biology of these disorders, as well as possible treatment strategies.

Another paper from the same group was published later in 2013 (Lee et al, Nature Genetics). This used a method for analyzing the heritability of medical conditions based on genome-wide data. Even if the power is not adequate to identify all of the gene variants individually, you can use the available information on gene arrays (small plastic chips that contain short sequences from every gene in the genome) to test whether or not you have captured some of the variation or not. It could be that testing every gene in the genome in this way would still not give you much information about diagnosis. This was thought to be the case for several years after these techniques were introduced. Many investigators felt that psychiatric disorders were simply too complex in their inheritance to be analyzed by the gene chips. There was too much “missing heritability” (evidence of inheritance from family studies that was not able to be tracked to variations at the gene level). This recent paper demonstrated convincingly that this idea is not true. The psychiatric disorders are analyzable at the level of individual gene variants and functions. We now can be confident that 25-40% of the reason that one person becomes ill with schizophrenia or major depression or autism while another person does not is related to common genetic variation that can be measured in the laboratory. We don’t yet know what all the pertinent genes do but we can anticipate that the answers will be available to us in the coming years. Part of the answer probably relates to calcium channel genes, as noted above.

There is another set of data from this paper that is tremendously important for our ideas of psychiatric diagnosis. For the past hundred years, we have clearly separated schizophrenia (a chronic disorder) and bipolar disorder (an episodic condition). There are different treatments for these conditions and different expectations for how well people will do in overcoming the symptoms. One of the lessons from the latest round of genetic analyses is that there is substantial overlap in the genetic vulnerability factors for the two disorders. The “covariance” between schizophrenia and bipolar disorder is 25-30%. Therefore we should expect that some of the disruption in neurobiological systems will be the same for the two disorders and some will be different. This is consistent with evidence from genetic linkage studies summarized by my colleague Dr. Berrettini some years ago and it is consistent with recent family studies as well. The new information, though, is more specific regarding the amount of overlap. It suggests that we should consider these two diseases similar in type and origin.

John I. Nurnberger, Jr. is co-editor of Principles of Psychiatric Genetics (out now).

Principles of Psychiatric Genetics

Medical Resources Strained in Japan

 March 17, 2011 — The devastating magnitude 9.0 earthquake and tsunami that occurred in Japan’s Miyagi prefecture on March 11 have caused a cascade of health and safety problems for survivors, including possible exposure to radiation from the region’s damaged Fukushima Daiichi nuclear plant. The disaster has strained medical resources on the ground, but it is unclear how many resources will be needed in the future.

“This is a very complex disaster, and it’s an evolving, ongoing situation,” Kristi L. Koenig, MD, director of the Center for Disaster Medical Sciences at the University of California–Irvine, told Medscape Medical News.

“The recovery phase of this disaster is going to be years and years and years,” she said. “They need people over the next many months to years to help, because the whole public health infrastructure is disrupted.”

Japan’s experience has been very different from Haiti, where a magnitude 7.0 earthquake struck in January 2010 and created a vast need for medical help. “In Haiti, the existing healthcare infrastructure was basically nonexistent,” Dr. Koenig said, “and the building codes for earthquakes were not anywhere near what they are in Japan.”

Unlike Haiti, Japan has well-organized civil defense teams that helped victims immediately until outside help was available, Dr. Koenig pointed out. These factors likely mitigated the injuries and deaths from the earthquake in Japan.

“Japan has significant emergency management capacity — one of the best in the world,” Margaret Aguirre, director of global communications for the International Medical Corps, told Medscape Medical News in an email.

Future Clinical Assistance May Be Needed Read more of this post

The Evolution of Disease in a Rapidly Changing World

Joy Henry is a blogger for An Apple A Day and a writer specializing in online nursing degrees for Guide to Healthcare Schools.

As humans evolve and the world they live in changes, the types and prevalence of disease they get changes as well. And while both environment and genes can be responsible for different diseases, a new study is shedding light on the crossroads between them. New research out of Stanford Medical School shows that as humans’ environments change quickly and drastically (which often happens), genes can become selected which simultaneously make them more fit and more susceptible to a certain disease. The old Darwinian mantra of positive benefit, positive selection becomes complicated when environment changes at an unprecedented pace. Read more of this post

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