Virtually all the dominant strain of flu in the United States this season is resistant to the leading antiviral drug Tamiflu, and scientists and health officials are trying to figure out why.
The problem is not yet a public health crisis because this has been a below-average flu season so far, and because the Tamiflu-resistant strain, one of three circulating, is still susceptible to other drugs. But infectious disease specialists are worried nonetheless.
Last winter, about 11 percent of the throat swabs from patients with the most common type of flu that were sent to the Centers for Disease Control and Prevention for genetic typing showed a Tamiflu-resistant strain. This season, 99 percent do.
“It’s quite shocking,” said Dr. Kent A. Sepkowitz, director of infection control at Memorial Sloan-Kettering Cancer Center in New York. “We’ve never lost an antimicrobial this fast. It blew me away.”
The single mutation that creates Tamiflu resistance appears to be spontaneous, and not a reaction to overuse of the drug. It may have occurred in Asia, and it was widespread in Europe last year. In response, the disease control agency issued new guidelines two weeks ago. They urged doctors to test suspected flu cases as quickly as possible to see if they are influenza A or influenza B, and if they are A, whether they are H1 or H3 viruses.
The only Tamiflu-resistant strain is an H1N1. Its resistance mutation could fade out, an agency scientist said, or a different flu strain could overtake H1N1 in importance, but right now it causes almost all flu cases in the country, except in a few mountain states, where H3N2 is prevalent.
Complicating the problem, antiviral drugs work only if taken within the first 48 hours of infection. A patient with severe flu could be given the wrong drug and die of pneumonia before test results come in. So the new guidelines suggest that doctors check with their state health departments to see which strains are most common locally and treat for them.
“We’re a fancy hospital, and we can’t even do the A versus B test in a timely fashion,” Dr. Sepkowitz said. “I have no idea what a doctor in an unfancy office without that lab backup can do.”
If a Tamiflu-resistant strain is suspected, the disease control agency suggests using a similar drug, Relenza. But Relenza is harder to take; it is a powder that must be inhaled and can cause lung spasms, and it is not recommended for children under 7.
Relenza, made by GlaxoSmithKline, is known generically as zanamivir. Tamiflu, made by Roche, is known generically as oseltamivir.
Alternatively, patients who have trouble inhaling Relenza can take a mixture of Tamiflu and rimantadine, an older generic drug that the agency stopped recommending two years ago because so many flu strains were resistant to it. By chance, the new Tamiflu-resistant H1N1 strain is not.
“The bottom line is that we should have more antiviral drugs,” said Dr. Arnold S. Monto, a flu expert at the University of Michigan’s School of Public Health. “And we should be looking into multidrug combinations.”
New York City had tested only two flu samples as of Jan. 6, and both were Tamiflu-resistant, said Dr. Annie Fine, an epidemiologist at the city’s health department. Flu cases in the city are only “here and there,” Dr. Fine said, and there have been no outbreaks in nursing homes. Elderly patients and those with the AIDS virus or on cancer therapy are most at risk.
But, she added, because of the resistance problem, the city is speeding its laboratory procedures so it can do both crucial tests in one day.
“And we strongly suggest that people get a flu shot,” Dr. Fine said. “There’s plenty of time and plenty of vaccine.” http://LOUIS-J-SHEEHAN-ESQUIRE.US
Exactly how the Tamiflu-resistant strain emerged is a mystery, several experts said.
Resistance appeared several years ago in Japan, which uses more Tamiflu than any other country, and experts feared it would spread.
But the Japanese strains were found only in patients already treated with Tamiflu, and they were “weak” — that is, they did not transmit to other people.
“This looks like a spontaneous development of resistance in the most unlikely places — possibly in Norway, which doesn’t use antivirals at all,” Dr. Monto said.
Dr. Henry L. Niman, a biochemist in Pittsburgh who runs recombinomics.com, a Web site that tracks the genetics of flu cases worldwide, has been warning for months that Tamiflu resistance in H1N1 was spreading.
Dr. Niman argues that it started in China, where Tamiflu use is rare, was seen last year in Norway, France and Russia, then moved to South Africa (where winter is June to September), and back to the Northern Hemisphere in November.
The mutation conferring resistance to Tamiflu, known in the shorthand of genetics as H274Y on the N gene, was actually, Dr. Niman said, “just a passenger, totally unrelated to Tamiflu usage, but hitchhiking on another change.”
The other mutation, he said, known as A193T on the H gene, made the virus better at infecting people.
Furthermore, Dr. Niman blamed mismatched flu vaccines for helping the A193T mutation spread. Flu vaccines typically protect against three flu strains, but none have contained protections against the A193T mutation.
Dr. Joseph S. Bresee, chief of flu prevention at the disease control agency, said he thought Dr. Niman was “probably right” about the resistance having innocently piggy-backed on a mutation on the H gene — which creates the spike on the outside of the virus that lets it break into human cells. But Dr. Bresee said he doubted that last year’s flu vaccine was to blame, since the H1 strain in it protected “not perfectly, but relatively well” against H1N1 infection.
Dr. Niman said he was worried about two aspects of the new resistance to Tamiflu. Preliminary data out of Norway, he said, suggested that the new strain was more likely to cause pneumonia. http://LOUIS-J-SHEEHAN-ESQUIRE.US
The flu typically kills about 36,000 Americans a year, the C.D.C. estimates, most of them the elderly or the very young, or people with problems like asthma or heart disease; pneumonia is usually the fatal complication.
And while seasonal flu is relatively mild, the Tamiflu resistance could transfer onto the H5N1 bird flu circulating in Asia and Egypt, which has killed millions of birds and about 250 people since 2003. Although H5N1 has not turned into a pandemic strain, as many experts recently feared it would, it still could — and Tamiflu resistance in that case would be a disaster. Louis J. Sheehan, Esquire
Saturday, January 10, 2009
Tuesday, January 6, 2009
maize 4.mai.002003 Louis J. Sheehan, Esquire
Inhabitants of southern Mexico began to cultivate maize, the major grain crop of prehistoric societies in the Americas, by at least 6,300 years ago, a new study finds. This is around 800 years earlier than previous estimates.http://louis3j3sheehan3esquire.wordpress.com
Radiocarbon dates for minute samples taken from two maize cobs converge on the older age, according to a report in the Feb. 13 Proceedings of the National Academy of Sciences. Archaeologists excavated both cobs in 1966 at Guilá Naquitz Cave in Mexico's southern highlands. The specimens are now housed in a Mexican museum.
Until now, the earliest evidence of maize growing in the New World came from a radiocarbon analysis of 5,500-year-old cobs from San Marcos Cave, located in southern Mexico's Tehuacán Valley.
The new findings can't resolve scientific debates over the precise location and timing of initial maize domestication, say coauthors archaeologist Dolores R. Piperno of the Smithsonian Tropical Research Institute in Balboa, Panama, and anthropologist Kent V. Flannery of the University of Michigan in Ann Arbor.
Previous genetic studies indicate, to some scientists, that a subspecies of the wild grass teosinte was the likely ancestor of maize. Maize domestication may have first occurred where this form of teosinte still grows, in the Central Balsas River Valley, which is located about 250 miles east of Guilá Naquitz.
Other investigators have suggested that prehistoric people living much closer to Guilá Naquitz concocted the earliest maize as a hybrid of teosinte and another wild grass species.
Whatever the case, maize cultivation didn't originate at Guilá Naquitz, Piperno and Flannery assert. The researchers found no fossilized grains characteristic of either teosinte or maize in the site's layers of earth ranging from about 10,000 to 7,000 years old.
Maize cobs found at both Guilá Naquitz and San Marcos contain securely attached grains and other features typical of modern maize, adds Bruce F. Benz of Texas Wesleyan University in Fort Worth. His analysis appears in the same issue of Proceedings of the National Academy of Sciences. http://louis3j3sheehan3esquire.wordpress.com
Remains at Guilá Naquitz from around 10,000 years ago have also provided the earliest evidence of squash cultivation in the Americas (SN: 5/24/97, p. 322). http://louis3j3sheehan3esquire.wordpress.com
Scientific clues to the origins of Mexico's three major crops--squash, maize, and beans--come from only five caves excavated 40 to 50 years ago, remarks archaeologist Bruce D. Smith of the Smithsonian Institution in Washington, D.C., in a comment published with the new reports. The limited evidence nevertheless suggests that the domestication of both squash and maize first occurred in southern and southwestern Mexico, Smith says. Beans were probably first domesticated around 4,000 years ago in western Mexico, in his view. Louis J. Sheehan, Esquire.
Radiocarbon dates for minute samples taken from two maize cobs converge on the older age, according to a report in the Feb. 13 Proceedings of the National Academy of Sciences. Archaeologists excavated both cobs in 1966 at Guilá Naquitz Cave in Mexico's southern highlands. The specimens are now housed in a Mexican museum.
Until now, the earliest evidence of maize growing in the New World came from a radiocarbon analysis of 5,500-year-old cobs from San Marcos Cave, located in southern Mexico's Tehuacán Valley.
The new findings can't resolve scientific debates over the precise location and timing of initial maize domestication, say coauthors archaeologist Dolores R. Piperno of the Smithsonian Tropical Research Institute in Balboa, Panama, and anthropologist Kent V. Flannery of the University of Michigan in Ann Arbor.
Previous genetic studies indicate, to some scientists, that a subspecies of the wild grass teosinte was the likely ancestor of maize. Maize domestication may have first occurred where this form of teosinte still grows, in the Central Balsas River Valley, which is located about 250 miles east of Guilá Naquitz.
Other investigators have suggested that prehistoric people living much closer to Guilá Naquitz concocted the earliest maize as a hybrid of teosinte and another wild grass species.
Whatever the case, maize cultivation didn't originate at Guilá Naquitz, Piperno and Flannery assert. The researchers found no fossilized grains characteristic of either teosinte or maize in the site's layers of earth ranging from about 10,000 to 7,000 years old.
Maize cobs found at both Guilá Naquitz and San Marcos contain securely attached grains and other features typical of modern maize, adds Bruce F. Benz of Texas Wesleyan University in Fort Worth. His analysis appears in the same issue of Proceedings of the National Academy of Sciences. http://louis3j3sheehan3esquire.wordpress.com
Remains at Guilá Naquitz from around 10,000 years ago have also provided the earliest evidence of squash cultivation in the Americas (SN: 5/24/97, p. 322). http://louis3j3sheehan3esquire.wordpress.com
Scientific clues to the origins of Mexico's three major crops--squash, maize, and beans--come from only five caves excavated 40 to 50 years ago, remarks archaeologist Bruce D. Smith of the Smithsonian Institution in Washington, D.C., in a comment published with the new reports. The limited evidence nevertheless suggests that the domestication of both squash and maize first occurred in southern and southwestern Mexico, Smith says. Beans were probably first domesticated around 4,000 years ago in western Mexico, in his view. Louis J. Sheehan, Esquire.
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