How lethal is Ebola? challenges statistics may be inflated survival

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How lethal is Ebola? challenges statistics may be inflated survival -

The Ebola virus that is causing the epidemic in West Africa is famous lethal. In previous outbreaks, he killed as many as 0% of those it infects. That's why the latest figures from the World Health Organization (WHO) "Status Report" look like they could be a rare glimmer of good news. Although the infection rate is increasing at an alarming rate, the report states that the mortality rate was 53% overall, ranging from 64% in Guinea to only 39% in Sierra Leone

But there is a snag .: the apparent low proportion of deaths probably depends more on how the health authorities calculate that the number on the deadliness of the virus or the quality of care patients receive. Indeed, the dramatic increase in cases in recent weeks is one of the main reasons why the rate of reported deaths appears to be artificially low.

There are several ways to calculate what officials call the "case fatality rate", or CFR, a disease outbreak. One of the simplest is to divide the number of deaths by the total number of cases. That is what the WHO in its recent CFR calculations.

But this method does not take into account that many living recently-diagnosed patients and poorly will not survive. So it underestimates the death rate. And this effect is exaggerated when an epidemic is growing rapidly. The calculation also lack of patients who were confirmed as cases of Ebola, but then left the hospital before being discharged, said Andrew Rambaut, an evolutionary biologist who studies infectious diseases at the University of Edinburgh in the UK -United. Many of these patients later died, but are not counted in the death statistics.

Another way to calculate the rate is to ignore current patients and count only patients who officially recovered and released from treatment or is known is dead. These figures seem to paint a picture more thinking. According to the update 7 September the Sierra Leone Ministry of Health and Sanitation, 268 patients were treated and released, and 426 confirmed cases of Ebola died. These figures suggest a fatality rate of 61%. But that's not quite true either, says Marc Lipsitch, an epidemiologist at the Harvard School of Public Health in Boston: Survivors may have long hospital stays means that patients who die. This would lead to a CFR that is artificially high.

A more accurate way to calculate the rate is to compare the outcomes of patients who were infected at the same time and wait long enough until all have either recovered or died. Rambaut notes that there were 23 survivors among the 77 patients included in a recent paper looking at the evolution of the virus. It is a CFR of 70%.

Christopher Dye, director of strategy for the WHO, said the organization is heading this method works and compiling data for each patient registered as a case. "We need reliable estimates," says Dye. "We want to know if CFR is different in this epidemic precedents in Central Africa [and] if different approaches to patient care in the current epidemic lead to different results."

Even this method is imperfect. in almost every home, the cases are missed because the patient never seeks care at a health facility, and therefore are not recorded in the statistics. These missed cases can potentially distort the CFR in both meaning, Lipsitch note. If many cases are relatively mild in which people recover without ever seeing a doctor then count on health care records overestimate the mortality rate. (This was the case for pandemic influenza H1N1 in Mexico, and experts suspect it is the case for MERS virus as well.) a Benin Ebola cases is less likely to go unnoticed in a Benin cases of influenza, Lipsitch said, but given the general lack of care health in the region, there could be a significant number of detected survivors.

on the other hand, researchers already know that many victims of Ebola never arrived at the hospital and died at home (often infecting family and other caregivers). This means that their deaths are not counted, the reduction of CFR.

Exactly how many unregistered Ebola deaths occurred will never be known. Health authorities keep track of suspect and probable cases, many people who died before they could be tested. Whether to include these numbers in the calculation of the CFR is another source of potential bias. And there are different models of tests in different regions: Some places have more tests on post-mortem, for example. "How to balance these prejudices is always the big question," says Lipsitch.

"We are not naive about the difficulties of CFR estimate," Dye wrote in an email. "I'm not yet ready to believe ... that CFR is much higher than in Guinea Sierra Leone. So say the data, taken at face value, but we need to exclude any possibility of ascertainment bias before believing this to be the truth "

* Ebola files :. given the current Ebola outbreak unprecedented in terms of the number of people killed and the rapid geographic spread, science and science Translational Medicine made a collection 'research articles and news on the viral disease available for researchers and the general public

* Correction, September 8, 1:53 p.m. :. the mortality rates in Guinea and Sierra Leone have been corrected.

Gut bugs can increase the effects of the flu shot

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Gut bugs can increase the effects of the flu shot -

Every year some unlucky people get the flu even if they had their chance season. One reason, according to a new study, could be their intestinal bacteria. The researchers showed that, at least in mice, a strong immune response to the vaccine against influenza is partly based on signals from the gut microbes. The findings could help explain variation in response to the vaccine and suggest ways to maximize its effectiveness.

The microbes that inhabit our body-collectively known as the microbiome, can influence everything from obesity risk for food allergies. Recent studies have also shown that the resident microorganisms affect how the immune system reacts to infection. For example, mice with depleted microbiomes appear to be more susceptible to the flu. But it is unclear what role the microbiome in the response to vaccines.

The new evidence emerged from a curious observation that researchers have found in a document of 2011. Bali Pulendran, an immunologist at Emory University in Atlanta, and colleagues were searching for genetic signatures in the blood of those injected with the inactivated influenza vaccine trivalent a mixture of three strains of influenza. They wanted to know if expression of specific genes in the white blood cells of the immune system in correlation with the amount of antibody specific to immunization in the blood, which indicates how well the immune system of a person responds to the shooting, and the degree of protection that person win against future infections. In a long list of genes associated with high immunization response, the researchers found an unexpected one: the gene that codes for a protein called Toll-like receptor 5 (TLR5)

"We thought this should be just one. coincidence, "said Pulendran. TLR5 is a sensor flagellin, a protein that forms the appendages of bacteria. Therefore a receptor that interacts with the bacteria in the gut have nothing to do with the body's response to a virus injected into the muscle? Perhaps, groupthink, B cells white blood cells that produce antibodies, receiving a signal from bacteria that stimulates their activity.

To explore this possibility, the researchers designed a new study using mice. They gave the vaccine against influenza to three different groups of mice genetically engineered to lack the TLR5 gene, the mice without germs, without microorganisms in their bodies, and mice that had spent four weeks water laced with antibiotics to obliterate most of their drinking microbiome.

Seven days after vaccination, all three groups showed significantly reduced levels of vaccine-specific antibodies in their blood to an eightfold reduction compared to control mice vaccinated, the online group reports today ' hui in immunity . The reduction was less marked day 28, antibody levels in the blood appeared to rebound. But when the researchers observed the mice lacking TLR5 the day 85th after vaccination, their antibodies seemed to have plunged again, suggesting that without this bacterial signaling, the effects of the vaccine against the flu over decay quickly.

researchers saw similar results when they gave mice a vaccine against polio, which as the vaccine against influenza, using an inactivated virus and does not contain so-called additives, adjuvants stimulate the body's immune response. Pulendran and his colleagues suggest that these vaccines, the lowest missing adjuvant rely more on bacterial signaling. (They do not see the same results with the live virus in the vaccine against yellow fever, for example.)

No specific types of bacteria seemed more important than another encouraging response to the vaccine. However, other experiments have shown an important role for macrophage-immune cells that exhibit virus pieces to activate B cells and can also recognize flagellin. Preferred explanation of Pulendran that flagellin is unable to pierce the lining of the intestine to circulate throughout the body and activate B cells and macrophages, amplification up to the production of antibodies. But where and how the interaction occurs "is a huge mystery," he said. "We do not have the complete answer."

However, what they do not know presents interesting opportunities for human vaccines. "I think that labor implications are wide enough," said David Artis, an immunologist at Weill Cornell Medical College in New York who was not involved in the study. "It tells us that the microbiome is an additional component [of the vaccine response] that we did not appreciate before. "He notes that people in industrialized countries seem more protection against vaccine against influenza that residents of developing countries, a phenomenon that could be partially explained by variations in their microbiomes, although genetics, diet, and previous infections probably also play a role.

He warned that the group would need to expose mice to flu after vaccination to confirm that the bacterial signals influence the vaccine induces resistance to the virus. But if it does, future vaccines could try to mimic the effect of the bacteria to trigger greater immune response. Several groups have explored as a possible flagellin adjuvant, if Artis suspect this is not the only important microbial protein in the game.

The findings also raise questions about the role of antibiotics in response to the vaccine, said Paul Thomas, an immunologist at St. Jude Children's hospital in Memphis, Tennessee. People taking antibiotics when they could see the vaccinated depressed antibody levels "for a long time after," he said. It suggests a follow-up study to measure the levels of antibodies in people who start antibiotic treatment before getting the vaccine against influenza. Pulendran said his group plans to do this for their next experience.

In Venezuela, the doctor fled after being accused of terrorism amid fever epidemic

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In Venezuela, the doctor fled after being accused of terrorism amid fever epidemic -

Eleven days after the news broke that an unknown disease killed eight people in the city of Maracay , Venezuela, doctors concluded that the deaths were caused by chikungunya, a mosquito-borne virus. Meanwhile, Angel Sarmiento, the doctor who first announced the death, fled the country after being accused of terrorism by President Nicolás Maduro.

Although officials initially speculated that the deaths were caused by an unknown hemorrhagic fever, six of the eight original death tested positive for chikungunya when samples were analyzed in laboratories nongovernmental, said Julio Castro, the Minister of health of the municipality of Sucre and professor at the tropical medicine Institute at the Central University of Venezuela (UCV). "We do not believe that these deaths are due to unknown or rare," he said Science Insider, adding that "I have no doubt" that chikungunya is responsible.

After arriving at the end of last year the Caribbean, chikungunya was swept Americas. As of September 19, the Pan American Health Organization reported 729,178 confirmed cases suspects and 9537 in the region. There is no vaccine or cure for the disease, which is similar to dengue fever and causes joint pain. It is fatal in about 1,000 cases.

Maracay The cluster of nine deaths reported between August 30 and September 15, has raised questions about how many people are infected. Fatal cases are "the tip of the iceberg," said Castro. In a press conference on Monday, Castro and two other professional-Gustavo Villasmil Health, Minister of Health of the State of Miranda and Manuel Olivares, a doctor hospital-UCV estimated that between 65,000 and 117,000 people in Venezuela are infected with chikungunya. They reached this figure by using the standards of the World health Organization for the calculation of the spread of epidemics. But it is much higher than the official statements published by the federal Ministry of health of Venezuela, which recognizes only 398 cases of chikungunya and three deaths.

many infectious diseases, including malaria and dengue fever, are the up in Venezuela, where the public health system was paralyzed by a lack of funds and medicine (including antipyretic medications that can help treat the symptoms of chikungunya). comments Sarmiento on deaths in Maracay seem was the straw that broke the camel when he came to criticism of the record of the government's public health, Villasmil said. Now, facing lawsuits, Sarmiento fled to an unknown destination in Central America. Villasmil and Castro remain in Venezuela, but left their homes after participating in the press conference, as a precaution against reprisals.

Does the sunshine database clarify or researchers links Industry cloud?

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Does the sunshine database clarify or researchers links Industry cloud? -

A federal database to publicly disclose payments to physicians companies went live this week, drawing attention to a touch of $ 3.5 billion given to doctors over five months last year. Although one purpose of the site is to shed light on potential conflicts of interest in research, the site may fall short of this goal.

The origins of the database back to a survey by Charles Grassley Senator (R-IA) in drug company consulting by university researchers. From 08, employees have alleged that Grassley a dozen psychiatrists and others failed to fully disclose to their employers hundreds of thousands of dollars in consulting revenue they received from companies. Public Health Service (PHS) Policy for the National Institutes of Health (NIH) grants the necessary researchers describe these payments to their institutions; but the totals reported below those reported by companies Grassley. In some cases, payments were companies whose drugs, the researchers studied, Grassley alleged (see full frame of a former member of staff Grassley here).

The Institute of Medicine (IOM) recommended the wider communication of the potential financial interests, and in 2011, PHS responded to stricter rules. IOM has also approved a proposal Grassley to require companies to report payments for display in a public database. Besides revealing payments that could influence the decisions of a doctor's prescription, medical schools have said such a database could help to cross-check that their faculty (those MDs, anyway) report under PHS rules.

the Grassley proposal became part of the Affordable Care Act, 2010, and opened payments database, managed by the Centers for Medicare & Medicaid Services ( CMS), entered into on 30 September. For now, it contains 4.4 million payments reported by drug companies and doctors to 546,000 devices and 1,360 teaching hospitals from August 2013 December 2013. They will free trips, meals, fees language, and gifts in search of funding. The links "does not necessarily indicate wrongdoing" and may include "benefits" CMS said in a press release, but their disclosure may "discourag [e] inappropriate relationships"

Up. now open payments got a mixed response. the investigative journalism group ProPublica warns of incomplete data and funding for ongoing research can not be included. (in addition, about 40% of payments are anonymised because CMS has not yet been able to match them with a personal doctor.) the site contains a little more raw huge spreadsheets that are difficult to find. CMS has promised to better search tools soon .

other problems include the research data itself. for example, payments include the dollar value of drugs offered by companies for clinical trials. For some medicines for cancer and hepatitis C that cost upwards of $ 100,000 per year, the total dollar value for only a few patients could be "staggering," wrote several researchers from Johns Hopkins University in an editorial September 30 online in Annals of Internal Medicine . They say the public may not be aware that payments are drug donations, not money going to individual researchers.

There are also not yet clear that the database will be a great help for institutions to audit faculty reports, said Heather Pierce the Association of American Medical Colleges in Washington, DC In addition to that the data are incomplete and in 2013, the payments appear individually posts, while institutions normally ask the faculty for the total costs of a company. There will also be differences because companies can include the dollar value of expenses such as hotel and transportation for a silver engagement speaking researcher never sees.

"There are many potential problems that can cause confusion or misunderstanding on the side of research payments," said Pierce.

She said that concerns about these differences have deterred some institutions to follow up on a suggestion in the PHS rules that show consulting revenue line researchers. Many are instead releasing it only on request.

Meanwhile, Pierce said, even with incorrect data in open payments' means either there may be a point for starting conversations "about why clinical researchers interact with industry, which "can be a very positive thing."

* fixed October 3, 8 am :. drug costs are $ 100,000 per year, not one months

Ebola vaccine trials raise ethical questions

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Ebola vaccine trials raise ethical questions -

Come January, up to 20 000 doses of an Ebola vaccine candidate could be ready for testing in the unprecedented epidemic running through West Africa. The vaccine and another whose development is 6 weeks behind could bring hope to a desperate population panicked. Indeed, some scientists believe that the epidemic has become so great that the vaccines will be vital to stop it. But tough questions are emerging about how to design clinical trials, expected to be the first to get the shots, and when to start mass production.

Until recently, many scientists said that by the Ebola virus, it would not be ethical to use the standard procedure for testing the efficacy of a vaccine: so-called randomized controlled trials ( ECR), in which some test subjects are assigned to a control group that does not receive the current vaccine. During a consultation organized by the World Health Organization (WHO) from 29 to 30 September, however, there was unexpectedly broad support for the design of the RCT after all, but not Médecins Sans Frontières (MSF ), which plays a huge role in the current epidemic.

September 2, a vaccine manufactured by pharmaceutical giant GlaxoSmithKline (GSK) Rixensart, Belgium, in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), which entered phase trials I, in which test the safety and immune responses in a small number of healthy volunteers. Preliminary results could be available as early as November. Similar studies for the other vaccine, developed by the Public Health Agency of Canada and produced by NewLink Genetics in Ames, Iowa, were launched on October 13, with the first results expected in December.

If vaccines do not cause damage and trigger the immune response Scientists hope to see WHO recommended to jump directly into the amount on Phase III efficacy testing in Liberia, Guinea and Sierra Leone, the three affected countries. It is an unprecedented extraordinary bet to move so quickly-but that WHO consultants say is justified by the extreme Ebola threat.

In the RCTs, half of the participants are randomly assigned to receive the experimental design and the other half a dummy, or placebo; ethicists say it OK if we do not know if the vaccine will do nothing, or cause damage. If a lot more people in the placebo arm develop the disease, the vaccine works. But animal studies suggest that Ebola vaccines could well provide protection; preventing the workers also face a deadly disease Ebola is unethical, some say.

The main alternative is a trial design known as stepped corner, which takes advantage of the unavoidable reality that a large-scale study can "t give everyone the vaccine at the same exact time. Stepped-wedge trials compare infection rates among people already vaccinated with those who have yet to receive the shots. "People are more comfortable" with this configuration because everyone in such a study given the vaccine against Ebola, says Barney Graham, a virologist at NIAID in Bethesda, Maryland, who attended the meeting of the wHO.

But at the meeting, Ripley Ballou, who heads the project vaccine against Ebola for GSK pleaded for RCT-although the placebo would be replaced by an "active control" a proven vaccine (eg, against hepatitis B), at least protect participants against another virus. an RCT, Ballou argued, provides the fastest way, the most acceptable to determine if a vaccine is safe and effective, and therefore would potentially save more lives.

Ballou describes a randomized study in which 2,500 people, probably health care workers receive the vaccine and 2,500 active control. He emphasized that his GSK team were many unknowns to wrestle with, including the risk of infection of health care workers, which they estimated at 10% per year in contact with Ebola patients. Assuming this is correct, and that the vaccine works at least 80% of the time, the researchers could be "absolutely confident" the effectiveness after 30 infections, which would be likely to occur within 3 months, Ballou said. A vaccine that was 60% efficiency could still give an answer with less than 60 infections.

This is much faster than a stepped design area, he said. Such a study will enroll participants at the same point in time, but would stagger the delivery of vaccines, for example, different Ebola treatment units. But researchers have yet to observe the different communities of the same start date, introducing delays and makes it more difficult to tell if the vaccine works. Infection rates can change over time, too, which complicates the analysis.

Ballou has not won more than MSF. "The efficacy studies in affected countries and more in populations at risk should not have a placebo or an active control arm that can not be defended ethics," says Annick Antierens, a participant in the meeting which oversees experimental products Ebola MSF. Antierens said MSF will support other designs efficacy trials of the vaccine against Ebola, but would not specify which. One idea is to simply distribute the vaccine to workers health, then do a "observational" study lacks a control group, but compared vaccination status in those who became ill in those who do not.

but most meeting participants sided with Ballou says Ira Longini, a biostatistician from the University of Florida in Gainesville. Longini changed his planned speech on the corner tiered design after Ballou spoke. "I suddenly saw a true double-blind trial with another vaccine that control was the way forward, "he said. Marie-Paule Kieny, an assistant director general of WHO, said "the meeting was very tense at times" but he was finally "broad agreement" on this design. "The Rip study made sense" said Kieny.

Jeremy Farrar, a researcher from the infectious disease that leads the Wellcome Trust in London, warns that people on the front lines of Ebola may disagree. An RCT may give faster results, but if it is simply unacceptable for trial participants, a stepped wedge design is preferable. "If you were there tomorrow and you're a health care worker, would you be ready to be in a control arm when the next 3 months, you will be looking after patients with Ebola? "Farrar request." I do not want us months of discussions on how best to handle this. "

Liberian nurses pick up a dead body waiting area of ​​a hospital in Monrovia

PHOTO :. EPA / AHMED JALLANZO

20,000 doses of the GSK vaccine that can be ready in January-double the previous-projections could be enough for several tests, which could allow different groups of participants to register in different models. "I'd do all these tests simultaneously," said Longini.

Before the tests are run, the health officials also need to decide who should participate. A WHO consultation in August recommended that efficacy trials first recruit health workers because they are at high risk and provide an essential service. But the last meeting "stopped talking about health care worker and started talking frontline helping," Ballou said, meaning that each of the doctors and nurses to janitors, people collecting the bodies, and gravediggers.

the next issue is when to intensify production. many researchers, including Longini, argue that the mass production of Ebola virus vaccines should begin positive phase I data exist to increase the likelihood of strokes will be widely available as evidence of the phase III study comes in. "I pull all stops, "says Longini. "I'll try to do 30 to 40 million doses to cover populations in West Africa risk." Farrar agrees. "We may regret that we must take these vaccines immediately if they are found not to be effective, "said Farrar," but I think that is a risk we must take. "

leaked documents reveal behind the scenes of Ebola vaccine problems

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leaked documents reveal behind the scenes of Ebola vaccine problems -

Extensive information materials from a meeting that took place today at the World Health Organization (wHO) have provided new details about exactly what he has to test, produce and finance vaccines for Ebola, which could be a potential game changer in the epidemic.

science Insider obtained materials vaccinemakers, governments and WHO has provided the 100 or so participants in a meeting on "access and financing" of vaccines Ebola virus. the documents precise figures on what until now have had little blurry academic discussions. and they make clear to participants-including representatives of governments, industry, philanthropies and NGOs that, although the testing and production grew at a record pace, thorny issues remain.

at the meeting, GlaxoSmithKline (GSK) Rixensart, Belgium, which has the most developing vaccine spelled how it could increase production in parallel with the safety testing and ongoing efficiency so the product could be ready for wider distribution by April if warranted. the company expects to have preliminary information in November in from phase I studies that analyze the safety and immune response in a small number of people not at risk of contracting Ebola. If these data are positive efficacy trials could begin as early as January in Guinea, Sierra Leone and Liberia, the countries of West Africa hardest hit by the epidemic.

Earlier discussions have suggested that the efficacy trials should recruit health care workers and first responders, such as those that are funerals or contacts pathway known infected individuals. WHO estimates that there are about 12 000 health workers in the three affected countries and another 17,500 "community" stakeholders.

GSK is planning two efficacy trials. The largest would be held in Liberia and involved 12,000 people. This study, which could begin in mid-January, would randomize half of the participants receiving the vaccine and the other half a placebo. The study may also have a third arm, GSK said: A vaccine manufactured by NewLink Genetics of Ames, Iowa, who has just entered Phase I studies in the United States. The US National Institutes of Health said it was interested in leading this study.

A second trial would begin simultaneously in Sierra Leone, Ripley Ballou, who heads the project GSK Ebola vaccine, said Science Insider. "One of the tests can fail for reasons of logistics," he said. "We have only one shot to get it right." The trial in Sierra Leone would not use a placebo group but would offer health workers at different points in time vaccine. This "stepped wedge" test could affect up to 8,000 people, and the US Centers for Disease Control and Prevention has had preliminary discussions with the affected countries about the staging of these studies. Although Guinea is also hit hard, he has the least infrastructure in place for a trial, said Ballou. "This would be the place most difficult to do a Phase III study."

GSK estimates (see table below, and here) it has 24,000 doses of its vaccine ready for testing in January efficiency. If it cranks production at full capacity before these tests are completed, the company could have 230,000 doses available in April and could gradually increase the capacity to produce more than 1 million doses per month by December 2015.

GSK has made small investments in increased production of the vaccine, and the table of projects that might be able to produce next year if all went outside and added several new production lines. the "at risk" noted by asterisks refers to the business of making quality control without having to wait for the regulators to repeat the tests.

In one database, GSK noted that a "critical issue" is called the filling capacity. GSK said there is a shortage of facilities that can fill vaccine vials under sterile conditions in a facility that meets the so-called biosafety level 2 conditions. He suggested that regulators relax their biosecurity requirements. If GSK only has to fill this will affect the ability of the company to produce other vaccines already on the market, including those that protect against rotavirus, measles, mumps and rubella, the document said.

the GSK paper also presents a number of proposals to make the first batches of vaccine available quickly, as running some of parallel quality control tests and changing the criterion used to prove the sterility of the vaccine to one that takes 14 days for a test that takes half the time.

further studies of the NewLink vaccine soon begin in Geneva, Switzerland, and Hamburg, Germany. A first batch of vaccine arrived in Geneva Wednesday, Marie-Paule Kieny, Assistant Director-General of WHO, said Science Insider. The Canadian government has donated 800 bottles of vaccine to the WHO, but is to send them in three separate shipments, Kieny said. "It just felt too risky to put all eggs in one basket," said Kieny, who has volunteered as subjects to test the vaccine itself.

Janssen, a division of Johnson & Johnson, described plans to speed the development of another Ebola vaccine strategy that has yet to enter human studies. a delegation of Russia planned to discuss Ebola vaccine being made, too .

a very detailed 28-page document by the Norwegian Institute of public health has offered "an estimate of crude oil costs" to intensify Ebola vaccine mass production. By these calculations, 27 million doses of vaccine would cost up to $ 73 million, and the cost of vaccination campaigns themselves add another $ 78 million to the bill.

Several analyzes posed regulatory issues and complex responsibility. The UK government has argued that "it is necessary to provide some form of relief from liability for producers and distributors of vaccines" and that WHO should coordinate discussions with regulators. The British government has also noted that "affected African countries will have the main role to allow or permit the use of experimental vaccines" and says "buy" these communities on clinical trials should be obtained as soon as possible.

regarding funding, the Government of the United Kingdom argues that a "multi-donor club" should pay for the development of vaccines "medium term". But for now, the UK said it will "unilaterally" cover the cost of purchasing vaccines in Sierra Leone, and asked the US government and France to make the same commitment to Liberia and Guinea, respectively.

in a planning document, the WHO reported several logistical problems, including "the ability to safely transport the intervention on the site of delivery, the existence of safe storage facilities a capacity of cold chain proper, the availability of sterile equipment to administer injections. "Ballou But the biggest question hanging over vaccine trials is the stability of the country. "The thing that will have the greatest impact is what happens to the trajectory of the epidemic curve," he said. "If current trends you progress two months into the future we are still in an environment where you can even consider doing a trial?"

* Ebola files: Given the current Ebola outbreak unprecedented in terms of the number of people killed and the rapid geographic spread, science and science Translational Medicine made a collection of research articles and news on the viral disease available for researchers and the General public.

Just a poliovirus left to go?

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Just a poliovirus left to go? -

the global eradication effort on the long-term polio years behind and shaken by reverses, got a shot of good news this week. Its leaders said the effort was probably eradicated the second of three varieties of the virus.

The feat, if confirmed, will mark the third time that a separate human pathogen has been erased by vaccination after smallpox and another strain of polio, the scientists write. "This is a very big deal ... that puts us much closer to eradication" of all three poliovirus said Chris Maher, director of the World Health Organization for polio eradication and interventions emergency in the Eastern Mediterranean region, which is not on the new paper. "Two of the three virus [are] down and one to go," he added. the new "auspicious" for the Initiative for global polio eradication (GPEI) accepts Walter Orenstein, an infectious disease specialist at Emory University school of Medicine in Atlanta.

the announcement on November 13 in Morbidity and Mortality Weekly Report ( MMWR ) comes with caveats. The document is entitled "eventual eradication of wild poliovirus type 3-Worldwide, 2012." "Since all the bumps on the road, we try to be careful ... "says Stephen Cochi, co-author and one of the leading scientists on the eradication of poliomyelitis in the uS Centers for Disease Control and Prevention (CDC ) in Atlanta. But "we believe that the evidence is pretty good," said first author Olen Kew, a virologist CDC ensuing whereabouts global virus since 1985.

Poliovirus comes in three varieties, or serotypes, each genetically distinct, with its own personality. Wild-type 2, for example, is more transmissible, whereas wild-type 3 tends to stay put. Wild-type 3 is the "most insidious viruses," Maher said because it causes paralysis in only about one in 1000 people it infects, compared to 0 for 1 wild type and may circulate undetected. The trivalent oral polio vaccine (OPV), which is a horse battle of the campaign is essentially three vaccines in one, and it works best against certain serotypes than others.

Wild-type 2 was the first to disappear worldwide in 1999 although it persists in what is known as a derivative form of the vaccine, created when the attenuated virus used in OPV reverts to its virulent form transmissible. For reasons that are not entirely clear, in most countries that have eradicated polio, wild-type 3 "verified" next to a number of years later, followed closely by wild-types 1, says Kew. In Vietnam, for example, the type 3 disappeared in 1993, and type 1 in 1994. India, the most recent country to eradicate polio, last saw type 3 virus in 2010; Type 1 held just one year. The eradicationists ardently hope the model will generally, and in recent years the GPEI went on a war footing, with more targeted vaccines and an influx of public health workers in infected countries.

The last two wild type 3 observations took place in Nigeria in 2012, where a | 11-month-old was paralyzed in the northern state of Yobe on 10 November. The last positive environmental sample was collected from waste water in Lagos the next day. Despite scouring the DNA evidence of wild poliovirus type 3 since "we can not find anywhere," says Kew. Although encouraged, Orenstein still want intense monitoring year for sure. "In my opinion, it is premature to celebrate the type of eradication 3. "

DATA: WORLD hEALTH thE

CDC scientists say they have made the announcement today because two years of intense surveillance are since the last observation. in addition to investigating stool samples of all cases of acute flaccid paralysis in the world to see if poliovirus is to blame, GPEI now testing environmental samples of wastewater in the footsteps of virus. This "would pick the same case without viruses," Kew said, as happened recently in Israel with wild-type 1 ( Science , November 8, 2013, p. 679).

genetic evidence also points to extinction, says Kew. Wild-type 3 has not disappeared suddenly. "It is not a binary event, you now, now you do not," says Kew. But over the years, the genetic diversity of this serotype decreased from 17 distinct genotypes in 1988 to only two in 2012.

The type 3 disappearance Nigeria adds the encouraging news from this country. He has not seen a trace of wild poliovirus in 3 months and have been only six cases this year. "I'm encouraged we will see a polio-free Africa by the end of the year," said Cochi. "The only uncertainty is persistent Borno, the northeastern state [the terrorist group] Boko Haram is most active."

The MMWR ad can also put even more pressure on the Pakistan, which has a runaway epidemic. the country now represents 85% of all polio cases in the world and constantly re-infect neighboring Afghanistan. with its ballooning housing account more than 235 this year, Pakistan is becoming a global "pariah," Cochi said. If the intensification of the GPEI strategy worked in Nigeria, with its unrest and insecurity, there is no reason it can not work in Pakistan he said, if the government finally gets serious about the eradication of poliomyelitis

* Fix (14 November 2014). in the original map, Guinea been incorrectly labeled as Liberia. the HTML and PDF versions were corrected.

Stem cells have potential for the treatment of rare diseases of the skin

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Stem cells have potential for the treatment of rare diseases of the skin -

Researchers have taken several steps to use stem cells to treat a rare genetic disease leaves people with skin so fragile that it blisters at the slightest touch. A trio of laboratory studies and animal reported today could help pave the way for a clinical trial to the disease called epidermolysis bullosa (EB).

While EB's quite rare, occurring in one in 20,000 births, about 500,000 people worldwide suffer from some form of the disease. It is caused by a defect in one of the many genes that encode proteins such as collagen, which connect the upper and lower layers of the skin. The genetic defect creates the fragile skin that is easily torn, which leads to painful blisters and sores. There is no cure; Doctors usually treat the symptoms by healing the wounds and treat infections. Those with severe forms of EB who survive childhood are also prone to skin cancer and often die of what their middle 40s.

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few years, researchers have tried gene therapy in a single EB patient, using a virus to add a corrective gene in skin cells cultured from that person, then leaves grafting of them on his legs. Although the cells repaired seized, the risks of the virus used in the test and the challenges of growing enough cells to cover a large area have led researchers to look for other options.

Several groups have now turned to induced pluripotent stem (iPS) cells, a cell type created by reprogramming adult cells back to an embryonic state. These iPS cells can be induced to grow in large quantities from various adult tissues that are genetically adapted to a person and therefore less likely to be rejected by the immune system that cells from a donor.

continue A team of Columbia University's approach iPS cells recently took advantage of the fact that some patients with EB have skin cells that lose somehow pathogenic mutations and become healthy cells. Scientists have converted some of these revertant cells "" in iPS cells, then the cells increased skin called keratinocytes that express collagen type missing in patients. When grafted onto the back of a mouse strain with a weak immune system would not reject cells from a different species, keratinocytes increased in human skin and produces the correct form of collagen. Using revertant cells in this manner for EB could avoid the risks of gene therapy and "be a little more simple," said study leader Angela Christiano.

But only about 20% to 30% people with EB have revertant skin cells, so that other groups have adopted a more traditional approach. in a second study, Stanford University researchers in Palo Alto, California, has created iPS cells from skin cells taken from three different EB patients lack collagen type studied by the Columbia team. They then determined the genetic defect in stem cells before turning them back into keratinocytes. These steps can potentially introduce deleterious mutations, and the original cells of EB patients can also lead to cancer-causing mutations. But the team has reduced this risk by genetic screening and the bank that iPS cells free of harmful mutations. The cells grew as skin grafts on mice up to one month before the dead cells.

None of these studies showed that the cells could help treat the disease in an animal with EB. But in the third study, researchers in the lab of Josef Penninger at the Institute Molecular Biotechnology of the Austrian Academy of Sciences in Vienna did just that by differentiating iPS cells from mouse skin cells with the same defect as the EB patients studied by the Stanford group. They then repaired the collagen gene; transformed cells into fibroblasts, another type of skin cells; and injected under the skin of diseased mice. These cells form the skin layers which express the correct form of collagen for 18 weeks.

Together the three documents, published today in Science Translational Medicine "should provide much optimism that this approach has great legs," says Anthony Oro, who co -dirigé Stanford study with Marius Wernig. Both the group and the Columbia team requested funding to launch iPS cell treatment trials in EB patients.

Although reports are promising, they also show the challenges of using these cells for skin disease, said stem cell scientist Lorenz Studer of Memorial Sloan Kettering Cancer Center in New York City. He notes that researchers have not yet found the right recipe to produce human skin cells live longer than a few weeks. "this therapy is still a little waiting until the field can achieve long-term graft," said Studer.

Jakub Tolar of the University of Minnesota, Twin Cities, who is also studying iPS and gene therapy for EB, highlights another problem. The approach of the skin graft will not treat the internal problems that many patients suffer from EB due to the effects of the disease on the lining of the intestine and esophagus. Tolar is working on a solution riskier but more complete: give a bone marrow transplant EB patients genetically corrected cells made using iPS cells. Yet he is impressed by the current trio of papers. "It is gratifying to see that they have taken to this point," said Tolar.

Why the bodies of men women abort during difficult times

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Why the bodies of men women abort during difficult times -

In hard times, several studies have shown, more girls are born than boys. Nobody knows why, but men should not fear being invaded by women. An analysis of old parish registers in Finland found that boys born in stressful times survive better than those born during the least difficult times. The work helps explain why women may have evolved a tendency to drop some bucks and could lead to a better understanding of miscarriages.

Men are more likely to die than women in the uterus. very cold weather tips, earthquakes, natural disasters, even the 9/11 terrorist attack on New York City exacerbate this difference, as months later, the ratio of boys to girls born may decline to well below typical ratio of 105 to 100.

biologists have long thought that women spontaneously abort male fetuses that are brittle, making room for new pregnancies and possibly a healthy baby. (Women are considered to have a better chance of reproducing than men in hard times, to the abortion does not make much sense of evolution.) Because of the scale of investment needed to raise children "there would be a great reward to be able to select the fetus and to raise that," said Ron Lee, an economic demographer at the University of California (UC), Berkeley.

the one result of this "slaughter" should be as healthy son born during tough times. in fact, in 06, health researchers population Ralph Catalano and Tim Bruckner of UC Berkeley found this trend in the data demographic of the Human Mortality Database. in these difficult years, a higher percentage of boys survived childhood. But Bruckner wanted to go beyond these statistics to see not only if these boys born in stressful times were healthier but if they produce more children than boys born during less stressful times. Such a scheme would provide an evolutionary explanation for such slaughter. It "could be adaptive," says Lee.

Bruckner turned to Virpi Lummaa, a biologist at the University of Sheffield in the United Kingdom who had centuries digitized Finnish church records that documented family history and recorded other data on every Finn born at that time. the researchers examined reports of newborns sex from 170 to 1870 and tallied the number of males survived infancy, an indication of how the fetal health was, and how many children they had subsequently that in turn hit puberty. they found that 16 percent of male survivors plunged sex of infants, with the late 18th century, fall of 79 men per 100 women. These men do better than their peers born in normal years, with about 12% more of them survive beyond the age of 1, Bruckner, Lummaa and colleagues report online this week in Proceedings of the Royal Society B . The data also indicated that in the most extreme cases, survivors have produced 8.7% more offspring than those born in the years when the number of male and female babies were almost equal .

The discovery "provides further confirmation of male suspicions [fetuses] are more vulnerable to miscarriage than women and that aborted fetuses are fragile," says the psychologist William James, an honorary research associate at University College London who was not involved in the work.

donation researchers' t know yet stress, such as hunger, that may have been experienced by pregnant women in unusual years. yet these data show that "the ambient environment during pregnancy shapes the quality of the men in their lives," said Bruckner. In general, men die 5 or 6 years earlier than women. "We try to understand the causes of gender imbalance in the life and contributing to the variance" in how long people live, he added. Identify what happens to the fragile men in utero is a first step in that direction.

the study is very interesting, Ken said Robert Smith, a biodemographer at the University of Utah in Salt Lake City, because "it covers a time when parents had no control over the sex of their children, "and therefore" the sex ratio reflects the basic interaction of biology and environmental stress. "comparing the survival of girls during normal sexual relationship years and predominantly female help ensure that men were really more robust and not just enjoying an environment that was better for all infants, said Smith. Also evaluates the survival of siblings would have strengthened the results. Lee and asks if there is no way to determine if the aborted fetus has led to better care of siblings or a healthy mother. Regardless, he adds, the work "demonstrates that the fundamental forces that arise early in life have [important] consequences."

Major cancer groups call for the e-cigarette research, regulatory sign

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Major cancer groups call for the e-cigarette research, regulatory sign -

A revealing the popularity of electronic cigarettes or e-cigarettes, which allow users to inhale nicotine vapor without other harmful chemicals, arrived late last year, the editors of the Oxford dictionaries said "vape" their word of the year for 2014.

Today, e- cigarettes got another notification type: Two of the largest groups of scientists and cancer treatment in the United States has asked the government to begin regulating "electronic nicotine delivery systems" and more research on the effects on the vaping health.

"While electronic cigarettes can reduce smoking rates and adverse health risks with it, we will not know for sure until these products are researched and regulated," said Paul said Peter Yu, president of the 35,000-member American Society of Clinical Oncology, in a statement. "We are concerned that electronic cigarettes may encourage non-smokers, especially children, from starting to smoke and develop nicotine dependence." His group was joined by the American Association for Cancer Research, which has more 33,000 members.

the joint statement approved the urgent need for further research on the health effects of e-cigarettes and using tobacco tax revenue to help finance studies. It also included a long list of actions recommended by the provincial and federal government agencies. They include requiring electronic cigarette manufacturers to register their products with the Food and Drug Administration (FDA) to identify chemicals and nicotine levels in various brands, and agree to help stop teenagers vaping.

in April 2014, the FDA issued a proposal to start regulating electronic cigarettes. The proposal would require FDA reviews of products e-cigarette and the leaders of force to stop an application for health benefits until the science is. The rule would also prohibit the distribution of free samples of e-cigarettes and sales of vending machines. Health warnings are required. FDA has not finalized the rules, however, and researchers and health professionals say they hope today's statement will highlight the need to move quickly.

"As someone who runs a treatment program for tobacco addicts, I would be able to approve the use of e-cigarettes as an alternative," said Michael Steinberg of the medical school Robert Wood Johnson at Rutgers University, New Brunswick, New Jersey. "But I can not do that because we do not know the risks involved, and we can not be sure that the transition to e-cigarettes really help people to stop smoking." Steinberg says he could reveal that smokers who start vaping tend to end up with two e-cigarettes and that flammable or nicotine product via e-cigarettes is toxic unexpectedly.

Some researchers fear that new rules do not go far enough, soon enough. neither the FDA's proposal or calls for a joint declaration today for a ban on television advertising by responsible e-cigarette, for example, says Stanton Glantz, director of the Center for Tobacco Control Research and education at the University of California, San Francisco. (Glantz, a frequent critic of the health claims made by electronic cigarette manufacturers, said he supports such a ban.) There also no e-cigarette regulation mention "flavors" such as menthol or fruity flavors, which were banned after they were linked to higher smoking rates among teens cigarettes.

Glantz also concerned that it could be years before the full FDA regulates devices. "It is a political and legal process particularly tortuous at the federal level," he said. The regulations may be easier to finalize at national and local level, he added, noting that several states and cities have already imposed restrictions. "I would look for progress at the local level," says Glantz. "I think in this case, the most important changes will begin at the bottom, not the top."

In the meantime, e-cigarettes are becoming more common. Small appliances, battery-powered first became readily available in the US in 06, sales increased to about $ 2 billion in 2014 alone. bars "vaping" where people talk of "vapers rights" arise in cities. Movie stars have announced their skills vaping on late into the television talk shows night.

last December, a survey released by the National Institute on Drug Abuse reported that 17% of high school seniors said they would vaped at least once a month, against 14% percent who admitted to smoking. Vaping among the 10 students, 16%, was more than twice the rate of smoking. tobacco control advocates found these alarming reports, arguing that vaping could become a "habit gateway" that could attract non-smokers to cigarette consumption.