Pandemic flu viruses brew for years before going global: Nature Newsfamily trees for pandemic influenza have revealed that components of deadly flu viruses probably lurk in humans
and other animals for years before they emerge as a worldwide threat to human health.
The work suggests that a more thorough characterization of circulating flu viruses could provide clues to an emerging pandemic before it hits.
According to results published this week in Proceedings of the National Academy of Sciences1, two genes from the 1918 influenza virus,
would have been present in human and swine flu viruses at least 6 years earlier. During the intervening years
swine and human flu viruses would have swapped genes with avian viruses, ultimately giving rise to the dangerous assortment of genes carried by the 1918 virus. This work suggests that the generation of pandemic strains
swine and human flu viruses and created family trees based on DNA sequence information. By estimating the amount of time it would take to accumulate the differences in DNA sequences found in human and swine viruses,
the researchers determined that a precursor to at least one 1918 flu gene was present in mammals before 1911.
The results run counter to previous hypotheses that the human 1918 flu strain had evolved directly from a bird flu virus2.
and then swapped genes with mammalian flu viruses before becoming a pandemic. Meanwhile, elements of the 1957 pandemic flu virus also thought to be a mosaic of human
and avian flu genes were introduced probably into human populations two to six years before the pandemic, the researchers found.
These analyses were completed before the current pandemic swine flu strain made its mark, but the researchers argue that their results have implications for future pandemics.
Results from 1918 and 1957 pandemic flu suggest that public-health authorities should track the sequences of all influenza virus genes in emerging strains
the authors argue, rather than focusing largely on the gene that encodes the haemagglutinin'protein,
Nevertheless, reliance upon patchy data from historical flu viruses has its limitations. Michael Worobey, who studies pathogen evolution at the University of Arizona in Tucson, says that his own analyses have suggested also that human
Swine flu shares some features with 1918 pandemic: Nature Newsas far as your immune system is concerned, the pandemic H1n1 (swine flu virus currently circling the globe bears an uncanny resemblance to an influenza virus that wreaked havoc nearly a century ago,
researchers have found. For months, it has been apparent that swine flu strikes the young more often than the old an unusual pattern that suggests older patients could have been exposed to similar viruses in the past.
A new study released today By nature suggests that people alive during the infamous 1918 influenza outbreak have the greatest protection against the current swine flu1.
The study also included experiments in a veritable menagerie of animals including mice, miniature pigs, ferrets and macaques.
In all but the pig, the virus yields an infection in the lungs that is more severe than would be expected from an average seasonal flu, according to Yoshihiro Kawaoka of the University of Wisconsin-Madison and his colleagues,
which reported that swine flu reproduces more aggressively and produces more severe disease in ferrets than seasonal flu (see Swine flu reaches into the lungs and gut).
Kawaoka's team observed this virulence in mice and macaques as well, but pigs showed no outward signs of disease
and found that those born before 1918 were more likely to produce antibodies capable of neutralizing the swine flu virus. That protection is somewhat counterintuitive:
But it is still possible that the immune response elicited by one virus can offer protection against the other (see Old seasonal flu antibodies target swine flu virus). Oddly,
At present, most swine flu infections are mild, and the severity of the present pandemic does not come close to the 1918 flu,
but experts worry that the new virus could become more virulent over time. Meanwhile, the virulence seen in the animal studies is disquieting,
Pandemic flu: People infected with the H1n1 swine flu virus who are otherwise healthy should not routinely be given antiviral drugs,
the World health organization (WHO) warned last week. Its recommendations are at odds with current practice in many countries,
He has led also research on allergy and infectious diseases at the National institutes of health. The FDA won powers to regulate tobacco for the first time in its 103-year history under legislation passed by Congress in June (see Nature 459,901;
Research HIV vaccine: An experimental HIV vaccine has shown moderate success at preventing infection by the virus. A US$119-million study involving more than 16,000 HIV-negative men
and women from Thailand found that a combination of two older drugs, which had failed to work individually, together reduced the risk of contracting HIV by nearly a third.
It's the largest step forward that's ever occurred in the HIV-vaccine field, says Dan Barouch of the Beth Israel Deaconess Medical center in Boston, Massachusetts.
Click here for a longer version of this story. Mars delay: The launch of Russia's Phobos-Grunt mission to study Mars
HIV vaccine doubt: Results of the largest-ever HIV-vaccine trial looked less impressive when full details were published formally last week (S. Rerks-Ngarm et al.
N. Engl. J. Med. doi: 10.1056/nejmoa0908492; 2009) than when they were outlined in a press release a month earlier.
In September, the trial was said to show that a vaccine combination reduced the risk of HIV infection by nearly one-third.
The week ahead 29 october â oe1 November Philadelphia hosts the 47th Annual Meeting of the Infectious diseases Society of America. go. nature. com/ykfvnw 29 â oe30 October
The board of the Global Fund to Fight AIDS, Tuberculosis and Malaria, the major funding channel for controlling these diseases, last week approved US$2. 4 billion in extra funding over two years.
which handles samples of H1n1 pandemic flu, and which earlier this year lost track of 22 vials containing harmless Ebola-virus genetic material.
and Infectious diseases to study chronic granulomatous disease, a rare genetic white blood cell disorder, and the University of South carolina to study Alzheimer's disease.
but in 1898, drought, pestilence and hunting left the Tsavo region of Kenya barren of the lions'favourite meals.
Nature News Liberia's caterpillar plague Panic struck Liberia in early 2009, after a plague of caterpillars struck villages around the country, munching trees
Tuberculosis funds: Tuberculosis research has seen funding jump in each of the past few years, but the rate of increase is dropping off.
So says a report released on 3 december by the Treatment Action Group, an AIDS research and policy think tank based in New york. Tuberculosis funding increased by 8%last year to US$510 million,
compared with annual increases of 13%in 2007 and 17%in 2006. The balance of funding is also shifting, from government agencies to philanthropic organizations such as the Bill & Melinda Gates Foundation.
It would become only the second disease that humans have wiped from the globe after smallpox,
Just as smallpox ripped through human populations for centuries, so too has reduced rinderpest drastically animal populations.
is caused by a morbillivirus a group of viruses that also includes measles. Clinical signs include fever, discharges from the eyes and nose, diarrhoea and dehydration.
By the 1970s, smallpox, too, was found only in the war-torn Horn of Africa, where the last case was isolated in Somalia in 1977.
The effort will make it only the second disease to be wiped from the globe the first was eradicated smallpox
The disease is caused by a virus called a morbillivirus a group that also includes the measles virus. Clinical signs include fever, discharges from the eyes and nose,
Anthrax case closed: Federal authorities in the United states announced on 19 february the conclusion of their investigation into the 2001 anthrax attacks,
which killed five people. They determined that biodefence researcher Bruce Ivins was the sole perpetrator;
such as analysis tracing mailed Bacillus anthracis spores back to a single-spore batch in Ivins's lab at the US ARMY Medical Research Institute of Infectious diseases in Fort Detrick, Maryland.
1998) that began the scare over a purported link between autism and the measles, mumps and rubella (MMR) vaccine.
to treat multiply drug-resistant tuberculosis simply isn't a good idea. The reason the problem arises at all is
Tough lessons from Dutch Q fever outbreak: Nature Newsthe chief veterinary officer of The netherlands has defended the country's decision to cull thousands of goats in an effort to control an unprecedented outbreak of Q fever.
The netherlands can't take a chance, Christianne Bruschke told Nature after a meeting in Breda a city near the heart of the outbreak.
Q fever, caused by Coxiella burnetii bacteria, is harboured in mammals, birds and even insects. It can trigger abortions in goats and sheep and causes flu-like symptoms and sometimes pneumonia in humans.
After more than 2, 200 confirmed human cases of the disease last year, the Dutch government slaughtered over 50,000 dairy goats on 55 of the country's nearly 400 farms in an effort to prevent the disease from spreading further.
project leader on Q fever in goats for the Central Veterinary Institute (CVI) in Wageningen, The netherlands.
Soil bacteria could yield drug to treat roundworm: Nature Newsa bacterial protein used in a common pesticide kills intestinal parasitic roundworms in mice
and may become a treatment option for humans, researchers say. Intestinal roundworms, including hookworms and whipworms, infect well over one billion people, lowering immune systems for HIV, malaria and tuberculosis and debilitating both physically and cognitively.
The new approach, published today in PLOS Neglected Tropical Diseases1, uses crystal proteins from the soil bacterium Bacillus thuringiensis (Bt.
Organic farmers have used Bt to kill insects for decades, and plants have been modified genetically with Bt genes
and is a common laboratory model organism for studying human diseases caused by roundworms, such as river blindness and elephantiasis.
Aroian's previous study2 using a type of human intestinal roundworm parasite to infect hamsters showed a 90%reduction in three doses of Bt.
which spreads dengue, chikungunya and yellow fever viruses, prefers blood meals over honey. The kinds of mosquitoes they trapped with this method are not necessarily the most important vectors for some viruses,
says Scott Weaver, who studies virus-mosquito interactions at the University of Texas Medical Branch in Galveston.
27 may News maker William Bishaithe tuberculosis expert will head South africa's Kwazulu-Natal Research Institute for Tuberculosis and HIV,
The World health organization (WHO) announced on 10 august that the world is no longer experiencing an H1n1 influenza virus pandemic.
said that countries were generally not reporting out-of-season outbreaks of the flu strain,
and that H1n1 would probably take on the behaviour of a seasonal flu virus. Margaret Chan,
500, the United nations this week warned of the spread of acute diarrhoea and waterborne diseases such as dysentery and cholera.
Peach hopes that the first phase of the cancer programme will pave the way for expanding genetic testing to more patients and other conditions, such as diabetes, AIDS and even psychiatric disorders.
Dengue control The release of male mosquitoes genetically engineered to be sterile can control dengue fever by suppressing the population of the insects that carry the disease, scientists at Oxitec,
Events Cholera in Haiti The escalating cholera epidemic in Haiti had claimed more than 900 lives and caused close to 15,000 infections by the start of this week, according to the Haitian Ministry of Public health and Population.
The cholera strain is most closely related to one from south Asia the US Centers for Disease Control and Prevention in Atlanta, Georgia, has said,
but from the scientific community's responses to them much as deaths from virulent flu come not from the virus but from the immune system's violent overreaction.
Anthrax report The US National Academy of Sciences has delayed releasing a long-awaited report on the investigation into the 2001 anthrax attacks, after a request by the Federal bureau of investigation (FBI.
TB diagnosis The World health organization (WHO) said on 8 december that a test that can rapidly diagnose tuberculosis (TB) was a'major milestone'for disease control.
Trend watch Growth of the global AIDS epidemic seems to have stabilized, said the UN Programme on HIV/AIDS (UNAIDS) on 23 november (see chart).
Numbers of new HIV infections have dropped, thanks in part to increased condom use and availability.
But there are still two new infections for every person starting treatment, said UNAIDS, and funds for prevention are inadequate and poorly allocated.
US$15. 9 billion was available for AIDS response in 2009, $10 billion short of 2010 needs,
Patient protection US President Barack Obama has asked his bioethics commission to review the recent discovery that US government-funded scientists intentionally infected subjects with syphilis in a study in Guatemala in the 1940s (see Nature 467,645;
Q-fever delay A report has found that the Dutch government took too long to respond to an outbreak of Q fever,
can trigger abortions in goats and sheep and cause flu-like symptoms and sometimes pneumonia in humans.
Nature Newspolicy Research People Business Trend watch Coming up Number crunch Policy Haiti's cholera fight Health officials have outlined plans for a proposed cholera vaccination
Transgenic chickens curb bird flu transmission: Nature Newsresearchers have made genetically modified chickens that can't infect other birds with bird flu.
The H5n1 strain of influenza which raged through Southeast asia a decade ago and has killed hundreds of people to date remains a problem in some developing countries,
where it is endemic. The birds carry a genetic tweak that diverts an enzyme crucial for transmitting the H5n1 strain.
We have more ambitious objectives in terms of getting full flu resistance before we would propose to put these chickens into true production,
It would be a bit like combination drug therapy for HIV, he says. Other experts point out that
even if the GM chickens carried full resistance to influenza, there are political and economic hurdles to their widespread commercial use not least the public's aversion to GM food.
What's more, flu viruses mutate quickly and are famous for evading vaccines. If made commercially available,
which includes genetic sequences that match up with an enzyme that influenza viruses use for replication and packaging.
but didn't pass on the flu to any of their uninfected cagemates. The researchers found that the amount of virus present in the infected GM birds was not significantly different from that in non-transgenic controls.
Animal diseases Livestock plagues are on the rise globally owing to increasingly intensive farming practices and the world's growing taste for meat and other animal products.
Livestock plagues are spreading: Nature Newslivestock plagues are on the rise globally, owing to increasingly intensive farming practices and the world's growing taste for meat and other animal products.
The warning comes from scientists at the International Livestock Research Institute (ILRI), based in Nairobi, Kenya,
A new infectious disease emerges every four months, and 75%of them originate in animals, according to ILRI figures.
The commission met in part to discuss last year's revelations that US government researchers secretly gave syphilis to hundreds of Guatemalan prison inmates in the 1940s (see Nature 467,645;
All had been disclosed publicly, unlike the syphilis experiments, but did not draw the condemnation at the time that they would today.
Virus sharing In the event of a future flu pandemic, member states of the World health organization (WHO) will send samples of flu virus to laboratories and drug makers around the world,
in return for greater access to any vaccines created. The deal announced by THE WHO on 17 april,
Nature Newspolicy Business Events Research People Trend watch Coming up Policy Smallpox stocks The World health organization (WHO) has failed to decide
when to destroy the world's last two remaining stocks of the virus that causes smallpox.
HIV scandal The last plaintiff suing Japan's government and five biomedical companies over HIV infection caused by tainted blood products settled last week for ¥28 million (US$340, 000) in damages.
Since 1989, nearly 1, 400 patients 墉 mostly haemophiliacs 墉 have sued after being infected in the 1980s by blood coagulants that were treated not to kill viruses.
Cornman, a geneticist for the Bee Research Laboratory of the US Department of agriculture (USDA) in Beltsville, Maryland, is trying to characterize the various pathogens that plague the honeybee (Apis mellifera), arguably the world's most important insect.
Research Cholera in Haiti The cholera epidemic currently raging through Haiti was introduced inadvertently to the country through faecal contamination of river water,
(which matches cholera strains circulating in Nepal). The outbreak 墉 the first in Haiti in nearly a century 墉 had killed by Mid-april almost 4,
whether to destroy smallpox stocks. go. nature. com/th3feu 16 19 may Eighteen Nobel laureates are participating in a symposium on global sustainability in Stockholm. go. nature. com/f7mow7 Â
Foot-and-mouth is a highly infectious disease that can have a huge impact on farmers'livelihoods.
says co-author Mark Woolhouse, an infectious-disease epidemiologist at the University of Edinburgh, UK. Only a small fraction of these actually had the virus,
if to other infectious diseases such as influenza. The difference in foot-and-mouth disease infectiousness predicted previously and that found through the experimental study shows a need for better evidence
The pathogens include bacteria and viruses that cause smallpox, the plague, anthrax, Ebola and foot-and-mouth disease.
Tellurium oxides were used as antimicrobial agents against diseases such as leprosy and tuberculosis before the development of antibiotics.
including Ebola haemorrhagic fever and severe acute respiratory syndrome (SARS), an outbreak of which killed more than 900 people in 2002-03.
an infectious-disease ecologist at Princeton university in New jersey who commends the project's focus. To control the increasing occurrence of diseases making the jump from animals to humans,
Anti-HIV gel fails An antiretroviral gel that seemed able to prevent sexual transmission of HIV to uninfected women has failed in a follow-up study.
The Microbicide Trials Network said on 25 november that it would drop the use of vaginal tenofovir gel from the VOICE study involving 5, 029 HIV-negative women in South africa,
Zimbabwe and Uganda after a routine data review found that it was no better than placebo at preventing HIV.
2010), the gel had cut the incidence of HIV by up to 54%.%Trials of tenofovir tablets in the VOICE study have failed also (see Nature 478,10-11;
Preventing HIV Pharmaceutical firm Gilead Sciences wants to sell anti-HIV drugs to healthy people,
and Drug Administration to sell its two-in-one antiretroviral medication Truvada (emtricitabine/tenofovir disoproxil fumarate) to people not infected with HIV.
Caution urged for mutant flu workwhy would scientists deliberately create a form of the H5n1 avian influenza virus that is probably highly transmissible in humans?
Surveillance of flu viruses could, they argue, allow health organizations to monitor birds and other animals for the mutations that would provide an early warning of a pandemic
More than a dozen flu experts contacted By nature say they believe that the work opens up important vistas in basic research,
But they caution that virus surveillance systems are ill-equipped to detect such mutations arising in flu viruses.
who heads the University of Minnesota s Center for Infectious disease Research and Policy in Minneapolis,
which are a good proxy for how flu behaves in other mammals, including humans. All five mutations have been spotted individually although not together in wild viruses.
provided that a mechanism is established to disseminate the data to flu researchers and public-health officials on a need-to-know basis. The US government,
39 flu researchers declared a 60-day pause in the creation of lab mutant strains of the H5n1 avian flu virus. The hiatus,
says Ilaria Capua, an animal-flu expert at the Experimental Animal health Care Institute of Venice in Legnaro, Italy."
H5n1 is far from being the only flu virus that poses a pandemic threat. But he believes that more extensive genetic surveillance could eventually pay off."
which the mutant flu research could provide immediate public-health benefits, Anthony Fauci, director of the US National Institute of Allergy and Infectious diseases, replies:"
) Wakefield's work posited a now-discredited link between autism and the combined measles, mumps and rubella (MMR) vaccine;
The DHS says that the NBAF is needed to develop countermeasures against bioterrorism a threat that resonates less now than it did immediately after the anthrax attacks on the United states in 2001.
See page 289 for more on the flu-virus debate. go. nature. com/pf7bwv20-24 february Marine scientists'responses to the Gulf of mexico oil spill in 2010 are discussed among topics at the Ocean Sciences Meeting in Salt lake city, Utah
Flu surveillance lackingin addition, the surveillance is sustained typically not, but instead is ad hoc and reactive,
But a flu virus that emerges anywhere, at any time, can threaten the entire planet.
lack of data, says Ian Brown, head of avian virology and mammalian influenza at the Animal health and Veterinary Laboratories Agency lab in Weybridge, UK.
Timely global surveillance of animal flu viruses is crucial not just for identifying pandemic threats,
and pig flu deposited in the US National Center for Biotechnology Information s Influenza Virus Sequence Database between 2003 and 2011.
and several large flu sequencing projects, including the Influenza Genome Sequencing Project a major initiative run by the National Institute of Allergy
and Infectious diseases (NIAID) to boost the sequencing of existing isolates. The analysis covered all subtypes of flu virus, not just H5n1.
That s important, says Malik Peiris, a flu virologist and surveillance expert at the University of Hong kong,
because"H5n1 is not the sole pandemic candidate, and low pathogenic viruses are just as likely, if not more likely,
to become pandemic. The number of avian flu sequences deposited in the database skyrocketed between 2003 and 2010,
before dropping off in 2011. The number of pig sequences deposited remained relatively flat from 2003 to 2010
The number of avian flu sequences from isolates collected in each year peaks in 2007 and plummets thereafter.
The Influenza Genome Sequencing Project is also helping by generating vast quantities of sequences it now accounts for half of all avian
An exception is the Centers of Excellence for Influenza Research and Surveillance a network created by the NIAID in 2007 to boost flu surveillance
which has a policy of releasing all sequence data within 45 days of its collection.
says Ilaria Capua an avian-flu researcher at the Veterinary Public health Institute in Legnaro, Italy, who champions greater availability of sequences5.
Just 7 of the 39 countries with more than 100 million poultry in 2010 collected more than 1, 000 avian flu samples between 2003 and 2011.
Surveillance of avian flu viruses is bad, but that of pig viruses is worse. Yet pigs are a serious pandemic risk:
they can be infected co with both human and avian flu strains, which means that they provide ample opportunity for gene swapping and, thereby,
679 pig flu sequences were collected between 2003 and 2011. Just three countries the United states, China and Hong kong  collected more than 1,
000 swine flu sequences each, and around 200 countries collected none at all. Five of those countries-Russia
In pigs, flu tends to be mild, so there is little economic incentive for surveillance. Moreover, the pork industry often doesn t want the negative image of having swine flu detected in its farms.
Research teams at Hong kong University, including one led by virologist Malik Peiris, are compiling one of the world's single largest sources of pig sequences.
a highly conserved set of six genes that allows the virus to swap genes with flu viruses from other species much more freely than the seasonal H1n1 that circulated before 2009 (see Pandemic 2009 H1n1 virus gives wings to avian flu).
globally changing the swine influenza virus landscape, says Peiris.""This certainly is a source of concern for public health.
and a well-structured and hygienic farming industry inevitably have fewer flu sequences to report,
or no sequences have poor veterinary systems and flu-prone farming systems, such as backyard farms and mixed poultry and pig farms,
which are often close to wild ducks and other flu reservoirs.""Proper geographic representation is lacking, says van der Werf,
Flu experts say that the dire state of surveillance could be turned rapidly around by, for example, creating a network of sentinel sites,
The problem is that no global body has overall responsibility for flu surveillance. The World health organization (WHO) runs a global network of labs for human flu surveillance
and selects human strains to be included in vaccines for seasonal flu. Monitoring animals falls to the FAO,
which tends to focus on food security, and the OIE, which looks mostly at animal health and trade.
Bovine TB disguised by liver flukebovine tuberculosis (btb) could be spreading across Britain because the most widely used test for the disease is ineffective
an infectious disease specialist at the University of Liverpool, UK, and an author of the paper, says the result helps explain why btb is still endemic across England and Wales."
showing that animals with preexisting tuberculosis had reduced sensitivity to the skin test when they were infected with liver fluke2.
and btb causes 10%of human tuberculosis deaths in Africa.""We know that a similar immune mechanism exists in humans,
says David Brandling-Bennett, the senior adviser for infectious diseases at the Bill & Melinda Gates Foundation in Seattle, Washington,
But the two largest players in malaria aid the Global Fund to Fight AIDS, Tuberculosis and Malaria,
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