A Rapid Response to Ebola

November 11th 2014 Update: Two manuscripts have now been posted to Speaking of Medicine and can be viewed here:

Social Pathways for Ebola Virus Disease in Rural Sierra Leone, and some Implications for Containment

What factors might have led to the emergence of Ebola in West Africa?

Original Post:

The ability to rapidly disseminate the findings of primary research as well as informed scientific assessment and opinion is critical in the face of public health emergencies such as the present outbreak of the Ebola virus.  At PLOS, primary research findings can be rapidly and effectively distributed through PLOS Currents: Outbreaks. The unmet need to provide expert commentary and insightful opinion on Ebola as rapidly has led PLOS Neglected Tropical Diseases to carefully select expert opinion, social science assessment, or topic reviews for public posting on Speaking of Medicine before formal and rigorous peer review.

The authors of manuscripts identified by the Editors as suitable are offered the opportunity to post their text with the understanding that, because of its quality and likely favorable review, is conditionally accepted for publication in the journal.  Authors are required to provide confirmation of authorship as well as financial disclosure and competing interest statements, which will be posted along with the text.

The Editors of PLOS Neglected Tropical Diseases are excited to provide a platform to make available much needed information publicly, openly, responsibly, and as quickly as possible.

For questions or further information, please contact PLOS NTDs Publications Manager Jeri Marie Wright at jwright@plos.org

Category: General | 2 Comments

Researchers Follow the Path of HIV and Prevention Interventions

Charlene Dezzutti from the University of Pittsburgh and the Magee-Womens Research Institute explains how HIV researchers are incorporating biomarkers and preclinical testing – featured in the PLOS Collection Advances in HIV Mucosal Immunology: Challenges and Opportunities – in their pursuit of an effective HIV preventative such as a topical microbicide gel or an oral pill containing anti-retroviral drugs or a vaccine.

Biomarkers are biological substances that mark the presence of a disease or condition in a person. For instance, cholesterol level is a biomarker for heart disease and CD4+ T cell counts or plasma HIV RNA levels are biomarkers for HIV disease progression. Biomarkers are important because they allow physicians to track an individual patient’s condition during treatment to better predict and improve health outcomes.

Image Credit: Artistic rendition of immune cells and potential HIV targets in the rectal mucosal. Yang, Ochoa, Preza & Anton, 2014

Image Credit: Artistic rendition of immune cells and potential HIV targets in the rectal mucosal. Yang, Ochoa, Preza & Anton, 2014

Likewise, biomarkers of product safety and efficacy would provide a tremendous benefit to the HIV prevention field because they would help identify preventatives that are safe and effective. Since newly developed experimental products cannot be tested in humans, models that accurately predict how humans would react – called “preclinical models” – are used. Because HIV in adults is usually transmitted sexually, with the exception of intravenous drug users, researchers have been targeting the tissues and routes that first encounter the virus to better understand the dynamic host-pathogen interaction.  Researchers are now working to develop and test animal and ex vivo tissue culture models to try and predict how these new HIV prevention products will work in people. The latest models use human mucosal tissue and secretions as well as non-human primates to mimic as closely as possible human exposures and potential responses.
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Category: General | 1 Comment

Urbanisation Up Close

Jocalyn Clark @jocalynclark discusses the urbanisation of the world’s population and its impact on global health.

Image credit: joiseyshowaa, Flickr

Image credit: joiseyshowaa, Flickr

Undeniably the world is urbanising. By 2050, according to the UN, the world’s urban population will almost double from its 2007 size of 3.3 billion to 6.3 billion people. The developing world will have more urban than rural dwellers by 2030. In terms of health, urbanisation gives rise to new threats and needs when delivering services.

Migration to cities usually means job prospects, educational opportunities, access to health care, and financial security for families. It can bring relief from conflict or land degradation. But it also brings problems associated with inadequate housing, overcrowding, air pollution, and road traffic. Both infectious (pneumonia, tuberculosis) and non-communicable (cardiovascular, diabetes) diseases increase with urbanisation.

I thought I knew big cities – the opportunities and the inconveniences – having lived in Toronto and London and travelled to many more across the developed and developing worlds. Then I moved to Dhaka, one of the world’s fastest growing cities (it grew an astonishing 45% between 2000-2010). Already 14 million people and densely crowded, by 2025 the UN predicts Dhaka will be home to more than 20 million people — larger than Mexico City, Beijing or Shanghai. Without the infrastructure, planning, or governance of those wealthier cities, Dhaka is like a poor cousin of mass urbanisation. Or, as a commentator recently said, it’s the ‘mega city of the poor.’

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Category: Global Health | 3 Comments

Ebola has Taught us a Crucial Lesson about our Views of “Irrational” Health Behaviors

Sara Gorman compares “irrational” reactions to the Ebola outbreak by Americans and West Africans.

As Ebola rears its ugly head in the U.S., there has been a lot of discussion about how afraid we really should be. While health officials have remained relatively calm, insisting in a tense congressional hearing that there is no need to panic, some members of the American public have gone in the opposite direction, proclaiming a state of emergency on social media channels such as Twitter and Facebook. Donald Trump has been an especially noisy voice on the topic on Twitter, demanding that Obama stop all flights to and from West Africa and proclaiming that Ebola is actually much more contagious than the CDC says it is. At the end of September, with the announcement of the first suspected case of Ebola in the U.S., Trump expressed panic on Twitter, writing:

trump 1

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Trump’s comments suggest not only a distrust of health authorities but also a kind of hysteria, with the use of the word “plague,” that is reminiscent of the infectious disease panic seen in many other outbreaks in American history, including SARS in 2003 and bubonic plague in 1924, the latter an outbreak that famously led to the frantic firing of thousands of Latino workers and destruction of homes in low-income Latino neighborhoods because they were seen as the “source” of the disease.

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Category: General | 7 Comments

The Price of Joining the ‘Middle Income Country’ Club: Reduced Access to Medical Innovation

On November 5, 2014, the WHO, WIPO and WTO will hold a joint symposium to discuss innovation and access to medical technologies in middle-income countries. In this post, Judit Rius Sanjuan and Rohit Malpani of Médecins Sans Frontières discuss the barriers to health care access for poor people in middle-income countries.

When people think about medical humanitarian aid, the usual association is with war zones and natural disasters, and the assumption is that the most critical medical needs are concentrated in the world’s poorest countries. That’s mostly right, but not entirely: while the needs in low-income countries remain huge, large—and growing—populations excluded from access to health care now live in countries classified as Middle Income (MIC). This shift presents enormous challenges, particularly in accessing new life-saving drugs and vaccines for diseases that take a disproportionately high toll on poor, marginalized populations.

For us at Médecins Sans Frontières (MSF), an organization providing emergency medical aid to people in acute need, the bulk of our resources are placed in countries classified as low-income economies. But over half the countries where we now have programs are classified as middle- or high-income economies. These programs range from short-term emergency responses, for example after last year’s Typhoon Haiyan in the Philippines, to aid for ongoing refugee emergencies in Iraq, Jordan, and Lebanon, to treatment programs for chronic and neglected diseases in India and South Africa.


Image Credit: Images_of_Money, Flickr

Today, more than 100 diverse economies are classified as MIC.  They are home to about 5 billion of the world’s 7.1 billion people, including more than three-quarters of the poorest people living on less than $2 per day, largely due to enormous and rising levels of inequality.

Yet the rising economic indicators that land a country in the MIC club in turn often exclude those countries from accessing the lowest prices for medicines and vaccines, due to tiered pricing and other market segmentation strategies employed by pharmaceutical companies, and increasingly by donors, governments and international organizations. In many MICs, health care costs are primarily paid out of pocket, so it follows that many poor and marginalized people have little or no access to care.
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Category: General, MSF | Tagged | 3 Comments

I’ve Got a (lot of) Little (check)lists

PLOS Medicine Editorial Director, Virginia Barbour, reflects on the publication of the CONSORT and PRISMA guidelines and reminds us of the importance of checklists to medical publishing.

Image credit: Oliver Tacke, Flickr.

Image credit: Oliver Tacke, Flickr.

Gilbert and Sullivan’s Lord High Executioner has, sadly given lists a bad name. Rather than tools of revenge, lists in healthcare, however, have the power to do much good. Atul Gawande’s book on lists has explained why they should be core to medical practice. I’d argue that in medical publishing too they are critical.

When Robert Boyle, one of the founders of the UK’s Royal Society, wrote the Spring of the Air he was probably the first to write in such a way that allowed other men (it was only men then of course) to repeat and test his findings.  In this way he was in turn one of the first to legitimize research by making it reproducible.

More than 300 years later we have a fully reproducible literature with everything fully reported, right? Wrong. There is a current crisis of confidence in research, with increasing and appropriate concern that many results, especially the most dramatic, often cannot be trusted. Contributing fundamentally  (but not exclusively, obviously) to this problem is that whole swathes of the medical and scientific literature are not described in sufficient detail that anyone else can even test. In medicine this crisis literally is life threatening; patients given treatments as a result of inadequately described studies may at best be treated sub-optimally, at worst harmed or killed.

However, in one important corner of the research endeavor a group of individuals, have, for many years now, been making a determined effort to change this poor reporting and PLOS Medicine is proud to have played its part in it. The CONSORT reporting guidelines for clinical trials and the PRISMA guidelines for Systematic Reviews and Meta-Analyses are, I’d argue two of the most important papers the journal has ever published. The premise behind both of these documents, and the checklists in them and the many other guidelines that we and other PLOS journals have published is very simple: tell us what you did so others can test it.

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Category: 10th Anniversary | 2 Comments

Voluntary Male Circumcision as HIV Prevention in Africa

PLOS Medicine Associate Editor Linda Nevin discusses the landmark publication, and striking impact, of the first randomized clinical trial of voluntary medical male circumcision, published in PLOS Medicine in 2005.

Image credit: (left) Sgt. Adam Fischman, US Army Africa & (right) Sterling Riber, MFDI for Jhpiego/Tanzania.

Image credit: (left) Sgt. Adam Fischman, US Army Africa & (right) Sterling Riber, MFDI for Jhpiego/Tanzania.

Since the 1980s, observational studies have shown that HIV infection rates in African tribal or ethnic groups that practice male circumcision are lower than rates in groups that do not. HIV protection by male circumcision has biologic plausibility; the removal of the foreskin reduces the covered, moist space in which the virus can incubate after sex. However, because ecological studies can never establish causality, the potential benefits of promoting male circumcision in African communities remained unclear past the year 2000. In 2005, Bertran Auvert and colleagues at the Hôpitaux de Paris, Boulogne, France published the first randomized clinical trial (RCT) of circumcision for HIV prevention, conducted in Orange Farm, a semiurban region close to Johannesburg, South Africa. In this trial, about 3,000 young, heterosexual uncircumcised men were randomly allocated to be circumcised upon enrollment, or 21 months later. In a planned interim analysis 17 months after the study was initiated, the authors observed a striking difference in incidence of HIV infection in the uncircumcised group (49 cases of 1582 participants) compared with the newly circumcised men (20 cases of 1546). The difference represented a statistically significant protection of 60% (95% confidence interval 32%–76%). At the request of the trial’s data and safety monitoring board, the trial was immediately stopped and all interested participants were circumcised.

This was broadly considered a landmark study in the field of HIV research. Its publication initiated robust debate about trial controls, blinding, covariates analyzed, and ethics; the paper has been cited in 998 scientific publications, and collected 99,867 page-views to date. At the time of publication, two other trials– in Kenya and Uganda– were underway, and researchers in the field waited on tenterhooks to see if the Orange Farm RCT results would be corroborated. They were. However, questions remained on the pragmatic front. Would a larger roll-out of a male circumcision program be effective across the diverse communities of Eastern and Southern Africa? Would circumcised men engage in risk compensation, the increase in unsafe behavior due to perceived protection?

Based on trial findings, Auvert and colleagues began a community-wide scale-up of voluntary male circumcision in Orange Farm in 2008. Their results from the 2008-2011 study period, published in PLOS Medicine in 2013, were a second landmark achievement. They observed an increased prevalence of circumcision (from 12% to 53%), a roughly 60% reduction in risk of contracting HIV among circumcised compared to uncircumcised men (consistent with the RCT), and no detectable increase in risky sexual behaviors among circumcised men. Using these numbers, the authors estimated that the VMMC scale-up reduced the 2011 prevalence of HIV in the community from a projected ~15% to ~12%.

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Category: 10th Anniversary | 3 Comments

The Truth about Standardized Packaging? Blow Some My Way

PLOS Medicine Associate Editor, Linda Nevin, discusses how a 2014 research article by Selda Ulucanlar and colleagues deconstructed advocacy documents submitted to the UK government by tobacco companies, and catches up with one of the authors for a Q&A.

Image credit: Rachel Chapman, Flickr

Image credit: Rachel Chapman, Flickr

As researchers, what is our duty to respond when corporate interests distort scientific evidence to influence policy? In a 2014 PLOS Medicine research article, Selda Ulucanlar and colleagues from the UK Centre for Alcohol and Tobacco Studies, University of Bath, used the lens of epistemology to search for truth, misleading arguments, and anything in between in expert testimony submitted to the UK government by British American Tobacco (BAT) and Japan Tobacco Inc (JTI). The testimony was submitted in response to a 15-question government survey issued in April 2012, inviting interested citizens, businesses and organisations to comment on a range of health and economic implications of standardised packaging (SP)—the strict specification of visual and physical pack attributes—of tobacco products. In their study, the authors checked the transnational tobacco companies’ (TTC) reference-based claims against the original sources to ascertain preservation of meaning, and assessed the scientific validity of TTC critiques of the evidence on SP. They found that the TTC reports misrepresented the evidence base in three ways: misquoting, mimicked scientific critique, and evidential landscaping (for explanation of these tactics, see the Editor’s Summary).

Much of the transnational tobacco companies’ (TTC’s) testimony was directed toward a seminal and influential paper in the field: Crawford Moodie and colleagues’ systematic review of 37 behavioural studies which, in sum, indicated that SP reduces the attractiveness and appeal of tobacco, increases the noticeability and effectiveness of health messages, and reduces the ability of manufacturers to mislead consumers about harmfulness to health. In the TTC critique of this review and the studies therein, Ulucanlar and colleagues explained, “Individual studies were examined in depth to determine whether any—on its own—constituted a warrant for SP and, following systematic deconstruction, none was found to be good enough to justify SP.” Based on this finding, the authors make an inspiring distinction between scientist and advocate: “In court, each piece of evidence (i.e., each study and the Moodie review) is treated as a separate piece of evidence and each needs to be undermined and discredited in turn until no evidence remains that could damage one’s client’s case. By contrast, in scientific work, it is essential that the extant research is synthesised and greater confidence in the findings established through the cumulative ‘weight of the evidence’.”

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Category: 10th Anniversary | 3 Comments

“Pulling Back the Curtain” on Lethal Injection

PLOS Medicine Associate Editor, Thomas McBride, reflects on the 2007 research article that investigated whether lethal injection consistently induces a painless death.

Image credit: Joseph Kranak, Flickr

Image credit: Joseph Kranak, Flickr

The December 7, 1982 execution of Charles Brooks Jr. in Texas marked the first use of lethal injection, conceived as a painless and more “humane” alternative to the electric chair. With the patient laying on a gurney, heart monitored by an ECG and an IV drip in arm, the new procedure certainly looked like a controlled death delivered by medical science. Over the next three decades lethal injection would become the most common form of execution in the United States and worldwide. But when reports of complications arose, the public and lawmakers began to question whether inmates were being forced to needlessly suffer. By 2006, 11 states had suspended executions while they considered changing the protocol. In a 2007 PLOS Medicine research article, Leonidas Koniaris and colleagues asked whether lethal injection truly delivers a consistently painless execution.

The article was an interesting choice for a medical journal. Despite appearances, lethal injection is anything but a controlled medical environment. Ending the life of a physically healthy person against his or her will is antithetical to medicine, which is why the technician who attaches the IV is not a doctor or nurse. The protocol was designed not based on experimental evidence, but the personal experience of Oklahoma state medical examiner Jay Chapman. Academic editor Clifford Woolf recalls the decision to publish was a “tough call, since it could be argued the paper better belonged in journal specializing in ethical or legal issues.” In an Editorial that ran in the same issue, the PLOS Medicine Editors expressed hopes that the data presented in the research article would convince US lawmakers that execution is inhumane.

The topic was also a departure from the norm for Koniaris and his colleagues, primarily cancer researchers. Lead author Teresa Zimmers recalls it was difficult to fit this research around their “day jobs” but that despite the sacrifices, they were “excited to add knowledge about the process and to help shape the debate.”

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Category: 10th Anniversary | 2 Comments

Quantifying the Dirty Nature of War

PLOS Medicine Senior Editor, Amy Ross, discusses the potential impact of the “Dirty War Index”, a tool developed by Madelyn Hsiao-Rei Hicks and Michael Spagat, to minimize civilian harm in areas of armed conflict.

Image Credit: valeyoshino, Flickr

While international humanitarian treaties, such as the Geneva Conventions, have sought to limit the barbarity of war over the past century and violence and deaths due to armed conflict have diminished dramatically in the last few generations, political violence within or between countries is still rife in many parts of the world. Media reports on civilian injuries and deaths in areas of armed conflict emerge on what seems to be a daily basis and, with often biased reporting of such events, it can be difficult to identify who is responsible for the worst of these harms. As data on these civilian deaths have become more readily available, a field of research has developed that attempts to quantify the impact of different war tactics on civilian deaths with the ultimate goal to minimize civilian harm.

In December 2008, PLOS Medicine published a Policy Forum by Madelyn Hsiao-Rei Hicks and Michael Spagat proposing a new tool, called the Dirty War Index (DWI), that was developed to systematically identify “rates of particularly undesirable or prohibited, i.e., “dirty,” war outcomes inflicted on populations during armed conflict”.

It uses a fairly basic calculation:

DWI = Number of “dirty,” i.e., undesirable or prohibited cases / Total number of cases × 100

where high DWI values can indicate indiscriminate warfare, especially dangerous weapons, or targeting of civilians.  As one of several examples in the paper, the researchers apply a “child casualty DWI” (Number of child casualties/ Total number of casualties) to weapons-casualty data from Chechnya between 1994 and 2005, to calculate the following ratios for different explosive devices: antitank landmines (34/223, DWI = 15), antipersonnel landmines (223/1,004, DWI = 22), booby traps (65/214, DWI = 30), and other unexploded ordnance (255/892, DWI = 29). They conclude that unexploded ordnance and booby traps are more dangerous to children than landmines in this setting.

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Category: 10th Anniversary | 1 Comment