Image Credit: Eric (HASH) Hersman

Three new articles were published this week in PLoS Medicine in the research and magazine sections.

Michael Delves and colleagues compare the activity of 50 current and experimental antimalarials against liver, sexual blood, and mosquito stages of selected human and nonhuman parasite species, including Plasmodium falciparum, Plasmodium berghei, and Plasmodium yoelii.

To read more on the effects of homocysteine on cardiovascular health, visit our most recent media release blog post.

Dejan Zurovac and colleagues discuss six areas where text messaging could improve the delivery of health services and health outcomes in malaria in Africa.

Remember you can comment on, annotate and rate any PLoS Medicine article and see the views, citations and other indications of impact of an article on that articles metrics tab.

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A comprehensive study in this week’s PLoS Medicine shows levels of the amino acid, homocysteine, have no meaningful effect on the risk of developing coronary heart disease, closing the door on the previously suggested benefits of lowering homocysteine with folate acid once and for all.

Previous studies have suggested that high blood levels of homocysteine might be a modifiable risk factor for coronary heart disease, but in a detailed analysis of data from 19 unpublished and 86 published studies, led by Robert Clarke from the Clinical Trial Service Unit and Epidemiological Studies Unit at the University of Oxford, the researchers found that lifelong moderate elevation of homocysteine levels had no significant effect on the risk of developing coronary heart disease. The study findings suggest that extensive publication bias, together with methodological problems, has played a role in previous suggestions linking homocysteine with coronary heart disease risk.

In their analysis, the authors found that in almost 50 000 individuals with coronary heart disease and 68 000 controls, people who had a variant of the MTHFR gene that is associated with 20% higher blood homocysteine did not have an increased risk of developing coronary heart disease. (The MTHFR gene is responsible for methylene tetrahydofolate reductase, which uses folate to break down and remove homocysteine).

The authors say: “The discrepancy between the overall results in the unpublished and the published datasets is too extreme to be plausibly dismissed as a chance finding. Some studies, particularly if small, might have been prioritised for publication by investigators, referees, or editors according to the positivity of their results and some may have been liable to other methodological problems that bias the average of all results. To avoid such biases, we chiefly emphasise the new results from the previously unpublished datasets. ”

The authors conclude: “The magnitude of the effect of publication bias is substantial and in addition to distorting the association of MTHFR with CHD [coronary heart disease] in published studies, publication bias may also help explain the discrepant findings recently reported for MTHFR and stroke.” Importantly, the lack of any link of disease with high homocysteine levels in the 50,000 unpublished heart disease cases with the MTHFR genetic variant is consistent with the null results from 10 large trials testing the effect on coronary heart disease of 5-years of folic acid treatment in 50,000 participants. Hence, both the genetic studies and the trials argue against the use of folic acid supplements as means if reducing coronary heart disease risk.

CONTACT:

Robert Clarke

Clinical Trial Service Unit

University of Oxford
United Kingdom
+44 1865 743743
robert.clarke@ctsu.ox.ac.uk

This media release was distributed to our press list under embargo before the article was published.

Image Credit: (L to R) Michelle Tribe; André Karwath; Paul Asman and Jill Lenoble

Selection of an appropriate model organism is a vital step in good experimental design. A number of articles published in PLoS Pathogens over the past month have touched on this topic…

The malaria research community has, over recent years, been engaged in a debate on the use of animal models in the research of severe malaria. This most recently culminated in a meeting of minds in Hinxton in the UK where researchers working with experimental animal models and those working with humans infected with malaria discussed recent research controversies. One of the key take home points from this discussion, which is described in a recent PLoS Pathogens Opinion article, was the need for greater communication between the two research communities to ensure that research in animal models will be applicable to the human disease state.

While it is no easy task to establish a suitable model for any disease system, things become even more complex when investigating multiple infections in the same organism.  Co-infection of tuberculosis (TB) is the single greatest cause of AIDS-related deaths. With the recent development of HIV mouse models researchers now have greater options for the modeling of HIV/TB co-infection. Previously, due to HIV’s specificity for human cells, the only model organism was the related Simian Immunodeficiency Virus (SIV) in macaques. The availability of new animal models means that even more consideration is required to select the best model for your research question.  Pawlowski et al. discuss some of the uses and limitations of these new models in a review published this week in PLoS Pathogens, which focuses on the immunological and pathogenic mechanisms of the synergistic interaction between HIV and TB.

And lastly, Desalermos et al. have produced an introductory guide to selecting the best invertebrate model host for your research. It’s written in the context of fungal pathogenesis but addresses topics such as mutant-availability, temperature sensitivity and virulence that would be applicable to bacteriologists and virologists as well. The guide outlines the questions you should pose when selecting the model to best fit your experimental hypothesis, because, as the authors point out, “no single model host can answer all scientific questions”.

Liz Flavall is a Senior Publications Assistant on PLoS Pathogens and holds a Master of Science degree in biochemistry. Her interests include the mechanisms of disease and the ethics of scientific research and publishing.

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Two new articles published this week in PLoS Medicine. There is also an update on recent news coverage on the homepage.

In a qualitative study reported by Olav Lindqvist and colleagues, the range of nonpharmacological caregiving activities used in the last days of a patient’s life are described.

Bohdan Nosyk and Julio Montaner argue that the cost-effectiveness of HAART roll out has been significantly underestimated because economic analyses haven’t yet taken into account the beneficial impact of HAART on HIV transmission.

Remember you can comment on, annotate and rate any PLoS Medicine article and see the views, citations and other indications of impact of an article on that articles metrics tab.

Image credit: National Archives of Records Administration

In December, PLoS Medicine published a paper by An Pan and colleagues, which focused on shift work and type 2 diabetes. The authors found that working night shifts on rotation over extended periods of time modestly increased the risk of type 2 diabetes and that this appeared to be partly mediated by body weight. The study has been viewed over 8000 times since publication and has attracted a great deal of press attention. Since the study was US-based, it was no surprise that much of this coverage came from American media sites such as USA Today, the Boston Globe and the Huffington Post (who reposted a report by Amanda Gardner at Health.com). Elsewhere in the world, however, the findings also made a significant impact, with the UK’s Daily Mail, Canada’s CBC News and the German magazine Focus all covering the paper.

Many media outlets opted for factual headlines reflecting the study’s findings, such as CNN’s ‘Night shift work may raise diabetes risk’ (also reposted from Health.com), and ‘Irregular Night-Shift Work Associated With Higher Diabetes Risk’ from the Wall Street Journal. The LA Times, however, chose the punchier “Shift work: Good for your pocketbook, bad for your health.” In her piece, reporter Melissa Healy explains that, although “these days, it’s just good to have a job”, if your job involves shift work your physical wellbeing could suffer. Alice Park at TIME also mentions shift work in light of the current economic climate, commenting that “the night shift isn’t usually anyone’s first choice, but in some professions — and in this economy — it can’t be avoided.” In a Perspective article published in PLoS Medicine on the same day as the research paper, Mika Kivimäki, David Batty and Christer Hublin state that “We are increasingly residing in a “24/7” society; thus, the option to eradicate shift working is not realistic.”

Just as the media storm generated around the paper by Pan and colleagues was dying down, at the end of December PLoS Medicine published an editorial related to the topic of how shift work affects health. The PLoS Medicine Editors discussed the link between shift work, diet and type 2 diabetes, arguing that unhealthy eating should be considered a new form of occupational hazard. Their article made international headlines, with some news sites such as TIME, the LA Times and the Huffington Post following up their stories on the Pan paper with coverage of the editorial. PLoS Medicine Chief Editor Dr Ginny Barbour, the lead author of the editorial, received multiple interview requests and is quoted extensively in pieces by ABC News, Toronto Star and The Checkup. A brief podcast reporting on the editorial is available on the Scientific American website.

Hopefully the media coverage that the interlinked papers received will have broadened public awareness that shift work can harm your health. The Checkup asks its readers: ‘Have you ever considered that the hours you work at your job can actually make you sick?” However, as the PLoS Medicine Editors outline, the findings of this study relate to a wider issue. Though we must all take responsibility for what we eat, the onus does not rest solely with the individual: “governments need to legislate to improve the habits of consumers and take specific steps to ensure that it is easier and cheaper to eat healthily than not. Could workplaces, specifically those who employ shift workers, lead the way (or be required to lead the way) in such a drive?”

Image Credit: Jon Rawlinson

This week, PLoS Medicine published four new articles, including a Perspective piece on a new Clostridium difficile Research Article.

A set of cross-sectional surveys by Robert Stewart and colleagues carried out in Cuba, Dominican Republic, Peru, Mexico, Venezuela, Puerto Rico, China, and India reveal the prevalence and between-country variation in mild cognitive impairment at a population level.

To learn morn about the Clostridium difficile infection paper by Sarah Walker and colleagues (and the related Perspective by Stephan Harbath and Matthew Samore) please view our latest Media Release blog post.

Edward Mills and colleagues argue that a more balanced approach to gender is needed so that both men and women are involved in HIV treatment and prevention.

Remember you can comment on, annotate and rate any PLoS Medicine article and see the views, citations and other indications of impact of an article on that articles metrics tab.

Image Credit: CDC

Contrary to current convention by which infection with the organism Clostridium difficile is regarded as an infection that is acquired by contact with symptomatic patients known to be infected with C. difficile, these may account for only a minority of new cases of the infection. These findings are important as they indicate that C. difficile infection, which can be fatal especially in older people, may not be effectively controlled by current hospital infection strategies.

In a study led by Professor Tim Peto of the John Radcliffe Hospital in Oxford, UK, and published in this week’s PLoS Medicine, almost 30 000 stool samples from nearly 15 000 patients were tested for C. difficile, with 4.4% (n=1282) found to be positive by specialised laboratory tests  (enzyme immunoassay and culture). With further tests (genotyping), the researchers identified 69 types of C. difficile and when linking this information to the clinical situation found that the majority of cases of C. difficile infection were not linked to known cases (66%) and only 23% shared the same type of C. difficile as a ward patient known to be infected.

The authors say: “In this endemic setting with well-implemented infection control measures, up to three-quarters of new [C.difficile infections] are not easily explained by conventional assumptions of ward-based transmission from symptomatic patients and so may not be targeted by current interventions.”

The authors conclude: “A better understanding of other routes of transmission and reservoirs is needed to determine what other types of control interventions are required to reduce the spread of C. difficile.”

However, in an accompanying Perspective article, Stephan Harbarth from the University of Geneva Hospitals and Medical School in Switzerland and Matthew Samore from the University of Utah School of Medicine in Salt Lake City, USA (uninvolved in the research study) note that given the methods used in the study, the research cannot definitively answer some important clinical questions, such as the amount of benefit accrued by blocking transmission from symptomatic C. difficile infection cases and the proportion of the C. difficile infections that are attributed to within-hospital transmission that actually represent already-infected individuals who come into the hospital. Harbarth and Samore say: “The study by Sarah Walker and colleagues cannot provide definitive answers to these questions because it has significant limitations with respect to both issues.” These authors recommend that more studies be conducted to fully answer these questions.

Please contact plosmedicine@plos.org if you would like to get in touch with the authors of this paper.

This media release was distributed to our press list under embargo before the article was published.

Four acts in 90 minutes. A tight script that does not leave time for clapping. Nine men in dark suits and one woman on stage. That one woman is Margaret Chan, Director General of WHO. One of the men is Bill Gates. The stage is Uniting to Combat Neglected Tropical Diseases (NTDs), an event convened by WHO and the Bill and Melinda Gates Foundation.

The first act: ‘Setting the stage’. This is the most comprehensive, coordinated action ever to address NTDs. “I have never seen so many competitors working together”, said Margaret Chan, referring mainly to the 13 large pharmaceutical companies present, but possibly also referring to the bilateral and multilateral donors. The prospect of elimination appeals to many.

An animation lays out what it is we are combating; ten circles, representing ten ancient parasitic infections which affect over 1 billion of the poorest and most neglected people. The ten circles move into two groups; seven versus three. For the seven – Guinea worm (eradication), lymphatic filariasis (elimination), leprosy (elimination), trachoma (elimination), schistosomiasis (control), soil-transmitted helminthes (control) and river blindness (control) – the battle can be geared up relatively easily. The tools and strategies already exist and for most of the seven these are simple and among the most cost-effective interventions in public health: periodic mass drug administration of cheap tablets and improving water and sanitation. But the other three, visceral leishmaniasis, human African trypanosomiasis (sleeping sickness) and Chagas disease, require new tools and strategies to make elimination/control possible.

In Médecins Sans Frontières’ medical programmes we see the need for these new tools and strategies every day: for rapid diagnostic tests, oral effective treatments and support to heavily under-resourced national control programmes. For sleeping sickness in particular, endemic countries are almost all failed and insecure states. ‘Sleeping sickness lives in the last village’, as a member of a national control programme in central Africa once said to my colleague. The national sleeping sickness programmes in most central African countries have few staff members, and worse, they can work only in parts of the year when there is money for fuel, transport and salaries. For sleeping sickness to be eliminated, enhanced research and development (R&D) and programmatic support along with access to current drugs are necessary. The actors at the London conference were offering only the latter. Now is the time to address the reality. It is urgent.

Act two featured making progress with existing tools, while act three ushered in innovation and new tools. ‘There is a today and there is a tomorrow’, said a CEO of a large pharmaceutical company. Today has a huge unmet need. Tomorrow is where R&D comes in. And, as another CEO said, ‘here is where the secrets are’. Indeed. The commitment made at the event by 13 large pharmaceutical companies to share and open up data and compound libraries is welcome news. But more attention went to announcements on branded drug donations; several existing donations will be increased or extended until 2020. Noble and useful actions – that should be seen in perspective. For example, MSD has, since 1981, annual sales of ivermectin for veterinary use of about $1 billion. Perhaps it is only fair to make it free for humans? For a few drugs, generic production would be better. No word on that in the script, though it was generic production (only) that made sustained and dramatic scale-up of access to antiretroviral treatment for HIV possible.

The last act: ‘Realizing the 2020 goals’. The story here was how to connect drugs and people, a simplified version of health systems strengthening; a score card needed to measure progress and impact; how to reach those most in need; the need to engage countries and coordination by ministries of health; creating a critical mass and tipping point. More questions than answers, but fair enough, this is just the start.

So, here is where we are. A common call to action and a road map to elimination and control of ten NTDs by 2020. History in the making, I hope. And I hope that the remaining essential steps will be executed with the same enthusiasm: include companies who develop diagnostic tools, get the political commitment of endemic countries, steer and heavily invest in national NTD control programmes, establish strong leadership of the initiative, measure progress and impact, build capacity to sustain the successes, and keep focus.

Rachel ter Horst, MSF

Rachel ter Horst is a Dutch physician who has worked for Médecins sans Frontières since 2003. She is currently serving as a medical advocacy advisor, based in Amsterdam.

Image Credit: James Gathany, Centers for Disease Control and Prevention

Author: Renata Santillan

The current issue of PLoS Neglected Tropical Diseases presents a new collection of articles on the use of genetically modified (GM) insects for controlling some of the most widespread infectious diseases. Articles from across the PLoS journals describe the technological advances these tools represent, the regulatory framework, and the societal dialogue that is necessary for their wide-scale application for disease control.

Diseases transmitted by insects form a huge burden on human and animal populations. Insect control has historically been one of many strategies for control of diseases such as dengue, malaria, and sleeping sickness. The debate on whether GM insects could be used for disease control began as soon as transgenic insects were first produced in the 1980’s. Since then several experimental releases of GM insects have taken place. These trials show promise for limiting the spread of many vector-borne diseases (most notably Dengue fever). Articles in this collection showcase different aspects of this new technology including development, environmental impact, and regulation. Public discussion of the science and application of GM insects is necessary as new developments bring potential wide releases closer to a reality.

In an Editorial, Drs. Michael J Lehane (Liverpool School of Tropical Medicine) and Serap Aksoy (Yale School of Public Health) state that GM insects “may provide great promise for new means of controlling diseases with a devastating impact on people’s lives. If so, then public acceptance is likely to be a key issue in their implementation.” With many countries considering open field trials of GM insects, a Viewpoint by Guy Reeves et al. examines the regulation process of the first 3 countries that have had field trials of GM insects. Commentary by John Mumford highlights that both national and international regulations are required due to factors regarding each country’s individual environmental risk to GM insects.  In a commentary from an industry perspective, Luke Alphey and Camilla Beech argue that “the agencies tasked to regulate GM insects have appropriately taken a cautious, thorough approach that allows progress towards realisation of the substantial benefits GM insect technology could potentially provide, while rigorously protecting the public and environment.”

The articles in this collection highlight many different points of view surrounding the research into GM insects. As the recent history of GM insect development demonstrates, public discussion is necessary as scientists continue to research GM insect technologies to control some of the world’s most devastating diseases.

Image Credit: Montage created by Pat Margis and Clare Weaver, PLoS

Four new articles published in PLoS Medicine today, starting with the monthly editorial.

In the January editorial, the PLoS Medicine editors review the journal’s contents in light of its mission and scope, and call for papers on specific topics.

In a cross-sectional analysis of WHO-AIMS data, Ryan McBain and colleagues investigate the associations between health system components and access to psychotropic drugs in 63 low- and middle-income countries.

In a before and after study, Johanna Westbrook and colleagues evaluate the change in prescribing error rates after the introduction of two commercial electronic prescribing systems in two Australian hospitals.

Teun Bousema and colleagues argue that targeting malaria “hotspots” is a highly efficient way to reduce malaria transmission at all levels of transmission intensity.

Remember you can comment on, annotate and rate any PLoS Medicine article and see the views, citations and other indications of impact of an article on that articles metrics tab.