Health Meaning

One might think that the first vaccine candidate to protect against malaria as cause of jubilation. But instead, the data on the candidate, known as RTS, S or Mosquirix have dribbled over the past two years, he was greeted with considerable-scratching head and some consternation about whether and how use.

The problem is that the vaccine developed by pharmaceutical giant GlaxoSmithKline (GSK), in partnership with the PATH Malaria Vaccine Initiative, does not work very well. In a large phase III trial, it reduced malaria episodes by about one third among young children in sub-Saharan Africa. That's well below the 50% efficiency expected at the beginning of the trial, and a far cry from the 95% efficiency of the dream vaccine manufacturers, leaving scientists and policy makers asking: What is good enough

part of the answer came today, as the European medicines Agency (EMA) has approved the use of the vaccine in African children aged 6 weeks to 17 month. The movement is a key first step on the way potentially complicated the deployment of the vaccine in sub-Saharan Africa. According to the fastest scenario, however, the introduction will not begin until 2017.

"We are very pleased with the outcome, said Moncef Slaoui, GSK vaccine president who for 30 recent years has been working alongside Joe Cohen and others to develop the vaccine. "the health of children in Africa will be transformed," he predicted.

But ask a malaria expert on what to do with RTS, S and they will tell you "it's complicated" There is no doubt that the vaccine candidate is a great achievement. Nobody never developed a vaccine against a parasite, especially one as cunning as Plasmodium falciparum , the main cause of malaria in Africa. And malaria is a huge problem, claiming nearly 0,000 lives a year , mostly children in sub-Saharan Africa. new tools to reduce the number of victims of malaria are desperately needed.

at the same time, everyone, including scientists at GSK wants some something better from a vaccine. at the end of the multicellular RTS, S trial, which involved all 16,000 children in eight African countries, the vaccine reduced malaria cases by 39% in young children 5 to 17 months and 27% for infants 6 to 12 weeks. Because vaccine efficacy decreases with time, trial tested three doses delivered 1 month apart, followed by a booster 18 months later.

"positive scientific opinion," The EMA as it is clumsily called, essentially concludes that the benefits outweigh the risks of using the vaccine in two age groups. The opinion is not a recommendation for use or formal approval is for countries to decide, but it opens the way to the World Health Organization (WHO) to make an overall recommendation on whether and how to use the vaccine. WHO should issue this recommendation by the end of the year.

The EMA review is part of an arcane regulatory process known as Article 58. As a service to poor countries that might not have the scientific expertise, the Committee of agency of human medicines reviewed the evidence in this case scientific hundreds of thousands of pages-with the same rigor as it would be in the review of a drug to be marketed in the European Union.

Then, in his review, WHO will address issues such as the real world cost-effectiveness, feasibility and public health value of the vaccine compared with other interventions. The result could go many ways. For example, WHO might recommend the use of the vaccine in all African countries affected by malaria only in areas where transmission is high. It could only recommend its use in toddlers whose effectiveness was higher, or in infants as well.

A second WHO committee decide whether the vaccine meets international standards of quality and safety and efficiency.

As with the EMA, the WHO recommendations are not binding, but poor countries the resources usually follow. And donors like GAVI Alliance vaccine, will not pay for the vaccine in poor countries without this recommendation.

Ultimately, it is up to regulators in each country to decide whether to approve RTS, S. Assuming that the WHO recommends the use of the vaccine, it will be a "difficult decision "for countries with limited resources, says Mary Hamel, an epidemiologist with the US centers for disease control and prevention and one of the principal investigators. David Kaslow, vice president of product development for PATH, agrees. "It is a bit unusual since the vaccine was introduced in the context of other interventions that also have costs associated with them," he said.

If the vaccine is not moving forward, scientists and policy makers agree it should be used only as a complement to other tools in the fight against malaria, such as bed nets and antimalarial drugs, not as a replacement. vaccine funding should not divert more effective interventions and research resources, WHO said today in a statement.

the opinion of the EMA is sure to fuel a debate over whether is preferable to wait a near-perfect vaccine against malaria or do better with what you have. in a comment to the BBC, the head GAVI Seth Berkley and Mark Dybul, head of the global Fund to explore the dilemma. "Mosquirix is ​​about 5 to 10 years ahead of all other vaccine candidates," they write, "and there is no guarantee any of them will be better. "

" With every vaccine, of course you hope for 100% protection, "said Slaoui, GSK and is already working on a second-generation vaccine. But he called the current vaccine protection "substantial". "If your child has three severe malaria a year instead of six, it will change their lives."

Each fall, millions of people roll up their sleeves for a vaccine against the flu, hoping to give their immune system a leg on influenza. But flu viruses are thousands of strains that mutate and evolve with the seasons, and the vaccine can not protect against all. Now, two groups of researchers have independently created vaccines that provide the basis for a long-sought shot that could protect against all types of flu.

"This is really cutting-edge technology," said Antonio Lanzavecchia, an immunologist at the Federal Technology Institute in Zurich Switzerland, which is affiliated to two studies. "There is still work to do, but this is a step forward and it is heading in the right direction. "

scientists are developing vaccines against influenza by predicting the most likely strains infecting a population. They use monitoring flu the year as well as field reports from the countries of the southern hemisphere to guess which strains are most likely to hit North America at the height of the flu season, December to March. But viral conjecture is a tricky business, and it is impossible to be 100%. This uncertainty makes the uneven protection, and that flu strains mutate during the season, vaccines are becoming less and less effective.

influenza vaccines stimulate the production of antibodies against pieces of dead virus. If the return of the virus, antibodies can recognize, attack and neutralize the threat. But because these vaccines are based on parts of the virus that evolve during a flu season, the protection is not guaranteed.

To solve this problem, two research teams independently focused on a protein called hemagglutinin, found on the surface of the H1N1 influenza virus. It has two main components: the head of the part of the virus that mutates and changes of the strain to strain and the rod, which is similar in most strains of influenza. The teams tried to remove the variable region of the head and hold the rod as a basis for vaccines. But hemagglutinin appears to be quite low. Once decapitated, the rod falls apart, and antibodies can not bind to it.

To anchor the stem headless, teams had different approaches. Researchers writing today Nature Medicine used a two-step method: They introduced a combination of mutations to stabilize the core of the hemagglutinin stem. Then they delimit a nanoparticle derived bacteria of the rod, which has reached the subunits of the protein as well as to hold it in the correct position. The other team, wrote today in Science applied a combination of mutations that realigned the subunits of the stem at the top. This was enough to sustain a functional structure for the vaccine.

When vaccinated mice teams, both groups saw a complete protection against the H5N1 virus, a deadly flu strain distantly related H1N1. In both studies, mice that did not receive the vaccine strains derived died, but the vaccinated mice all survived. In other experiments, anchoring the nanoparticle vaccine have shown partial protection in ferrets, while the other vaccine showed partial protection in monkeys. Two of six ferrets vaccinated became ill and died, compared to a death rate of 100% for unvaccinated ferrets. None of the monkeys died, but those who were vaccinated were significantly lower than their unvaccinated mates fevers.

"The [experimental] designs were different, but the end results were very similar and highly complementary," said Ian Wilson, co-author on the science paper and a structural biologist and computer at the Scripps research Institute in San Diego, Calif. "it is a promising first step, and it is very exciting to see this research to fruition." The authors of both studies say the next step is expanding the protection to other flu strains, namely H3 and H7.

A virus that had long been spliced ​​into the human genome may play a role in amyotrophic lateral sclerosis (ALS) the deadly muscular degenerative disease that paralyzed baseball great Lou Gehrig, and eventually took his life. This is the controversial conclusion of a new study, which found levels of human endogenous retrovirus K (HERV-K) higher in the brains of 11 people who died of the disease.

"This is certainly an interesting and provocative work," said Raymond Roos, a neurologist at the University of Chicago in Illinois who treats and studies of ALS, but has not participated in the conclusion . yet even scientists behind the work caution that more research is needed to confirm the link. "I'm very careful to say HERV-K does not cause the disease but can play a role in the pathophysiology," says study leader AVINDRA Nath, a neuroimmunologist the National Institute of neurological disorders and Stroke in Bethesda, Maryland. "The thing is damn in the chromosomes to start. It will be very difficult to prove causation."

There was another retrovirus, HIV, which led to the first Nath suspect a link between the virus and ALS. In 06, it was to help a patient to control his HIV infection with antiretroviral drugs when he noticed that the SLA of man has also improved. "It intrigued me, and I looked in the literature of ALS and saw that people had reported they could see reverse transcriptase in blood." reverse transcriptase, an enzyme that converts RNA to DNA is a hallmark of retroviruses, which use to insert copies of their genes into the chromosomes of their host.

No study had ever found a convincing retrovirus in patients with ALS. But the researchers only looked at viruses that came from outside the body. About 8% of the human genome consists of endogenous retroviruses "" such as HERV-K, which are likely the remains of old viruses. These retrovirus initially infected an egg cell or human sperm and entrenched themselves in the chromosomes, which allows them to spread from one generation to another. The finally deactivated DNA mutations retroviral incorporated.

In 2011, Nath and colleagues reported they had found increased levels of expression for HERV-K gene in the brains of autopsied people who died of ALS . Their new study, published online today in Science Translational Medicine , is based on previous work with analyzes of more brains and evidence supporting tube experiments and mouse test.

In about 10% of people with ALS, someone else in the family has the disease, suggesting that it comes from an aberrant gene inherited. Nath and colleagues focused instead on what is known as sporadic ALS: where people have no family history of the disease. Strengthen their 2011 study, the team found high levels of three different HERV-K genes in the brain autopsied ALS. Researchers are not isolate the virus itself, which notes Nath is logistically difficult because it would have to analyze the brains "fresh" soon after death.

Researchers have also shown in test tube experiments that the addition HERV-K genes to neuronal cultures led to a significant decrease of the cells. Using as the electroporation technique known to insert a HERV-K gene in the brains of embryonic mice, the researchers showed neuronal lesions similar. The researchers then developed mice that express HERV-K gene in all neurons. Again, the gene leads to neural mayhem, and the animals had similar muscle problems to what is observed in patients with ALS.

retrovirologists Some warn that the evidence remains thin that endogenous virus causes ALS. John Coffin who studies HERV-K at Tufts University in Boston, notes that high expression levels of genes of this retrovirus found in many conditions, including breast cancer, multiple sclerosis, schizophrenia, and melanoma, but none has been conclusively shown to be caused by it. "There are many documents like this," said Coffin. "The upregulation of the endogenous virus group is a very common finding."

Coffin said "group" because there are about 0 different HERV-K, and that's another concern that has labor laboratory Nath: the study does not show that all ALS patients have exactly the same version of the virus in their brains "I. am quite prepared to accept that there is toxicity, but I'm never quite sure what to do these kinds of experiences, "said Coffin. He notes that in the 1970s and 1980s, so many researchers wrongly asserted that exogenous human viruses-those who move between people or tumors commonly, humans and animals caused that they became known as "virus rumor." "There is a good amount of buzz around virology endogenous retroviruses responsible for the disease."

Even Nath stressed that he wants other labs to confirm the findings of his team. "I work with HIV for many years, and I am aware of the pitfalls, and that's why we wanted to ensure that we were very, very careful before we stuck our necks out," said Nath. "It took us 10 years to produce this document."

Nath is launching a clinical study to evaluate the impact of treatment of ALS patients who have high levels of HERV-K genes expressed in blood with a combination four antiretroviral drugs used to treat HIV infection. The Phase I study will mainly determine if treatment for 24 weeks can lower gene expression to undetectable levels HERV-K, but Nath also monitor the progression of the disease. Whether the anti-HIV drugs will even have an impact on HERV-K does not know. Drugs targeting reverse transcriptase and protease enzymes, both viruses depend, but there are differences between the HERV-K versions and HIV.

Coffin, who warns that antiretroviral toxicities have said the trial is madness. "The reason for this is non-existent," he said. Nath counters that there are about 40 cases described in the literature of ALS patients taking antiretrovirals, but it is difficult to make sense of these reports, about half of the claimed improvements. "No one has ever made a systematic study," he said.

Again, Nath allows increased expression of HERV-K genes in ALS patients may simply be the result of something else that causes real damage. "The reasons for skepticism are very valid," Nath said. "We could be wrong too."

India has the largest number of blind children in the world, many of which are born with cataracts. A simple surgery early in life can reverse this condition. But in India, poverty and lack of access to health care shall record most children with congenital cataracts to a life in the dark. Prakash project was launched in 04 to provide cataract surgery in older children and young adults who were considered beyond help because they passed a critical age when the vision develops in the brain. The project has so far provided nearly 500 children and young adults in the light, and in the process revealed some surprising insights into how the brain learns to see. Read the full story here.