Saturday, October 15, 2005

Bird flu virus reported to resist Tamiflu

More popular press stories on drug resistance in bird flu:

"An avian influenza virus isolated from an infected Vietnamese girl has been determined to be resistant to the drug oseltamivir, the compound better known by its trade name Tamiflu, and the drug officials hope will serve as the front line of defense for a feared influenza pandemic. [Science Blog - Science News Stories]"

The New England Journal of Medicine has a recent free article summarizing our current state of knowledge titled Avian Influenza A (H5N1) Infection in Humans:

"High-level antiviral resistance to oseltamivir results from the substitution of a single amino acid in N1 neuraminidase (His274Tyr). Such variants have been detected in up to 16 percent of children with human influenza A (H1N1) who have received oseltamivir. Not surprisingly, this resistant variant has been detected recently in several patients with influenza A (H5N1) who were treated with oseltamivir."

This is not to say, however, that we have no other neuraminidase inhibitor tricks up our sleeves.

Monday, March 14, 2005

WHO warns of human bird flu mutation

ABC News Online--WHO warns of human bird flu mutation.:

" The World Health Organisation (WHO) says the bird flu virus may be changing into a form that humans can pass on.

The WHO is worried that bird flu, which has killed 47 people in Asia, could mutate into an easily spread form that sparks the next influenza pandemic.

The organisation has identified a cluster of human bird flu cases among relatives and possibly health workers in Vietnam.

"Such cases can provide the first signal that the virus is altering its behaviour in human populations and thus alert authorities to the need to intervene quickly," the WHO said in a statement.

The main concern of the WHO was a series of cases of the deadly H5N1 bird flu virus in a family in the northern Vietnam province of Thai Binh and the possible infection of two nurses who cared for one of the patients.

The WHO also says it has received confirmation of an additional 10 cases of human infections from Vietnam's Health Ministry.

The new cases were detected in early March or through re-examination of older cases, some of which dated back to late January and three of which had been fatal, the WHO said. "

See the WHO web site for details.

Wednesday, February 16, 2005

New Manifestations of Avian Influenza A (H5N1)

NEJM--Fatal Avian Influenza A (H5N1) in a Child Presenting with Diarrhea Followed by Coma:

" In southern Vietnam, a four-year-old boy presented with severe diarrhea, followed by seizures, coma, and death. The cerebrospinal fluid contained 1 white cell per cubic millimeter, normal glucose levels, and increased levels of protein (0.81 g per liter). The diagnosis of avian influenza A (H5N1) was established by isolation of the virus from cerebrospinal fluid, fecal, throat, and serum specimens. The patient's nine-year-old sister had died from a similar syndrome two weeks earlier. In both siblings, the clinical diagnosis was acute encephalitis. Neither patient had respiratory symptoms at presentation. These cases suggest that the spectrum of influenza H5N1 is wider than previously thought. "

Thursday, December 9, 2004

NEJM -- The Genetic Archaeology of Influenza

NEJM -- The Genetic Archaeology of Influenza:

" "Different strains of influenzavirus have different pathologic effects. For example, infection by the so-called Spanish influenzavirus caused more than 20 million deaths in 1918 and 1919, many of which were due to hemorrhagic pneumonia. To identify the critical components of this virus, mouse-adapted influenza A viruses (Panel A) were modified by Kobasa et al. so that these viruses expressed the form of hemagglutinin encoded by the gene of the 1918 Spanish influenza strain (HAsp), alone (Panel C) or in combination (Panel B) with the form of neuraminidase encoded by the gene of the 1918 Spanish influenza strain (NAsp). They concluded that the HAsp protein is critical to the enhanced cytokine production, inflammation, and hemorrhagic pneumonia that characterized this virulent influenza." "

" "This new study has important clinical and epidemiologic implications. Assuming that the mouse model at least partially reflects the important factors in the virulence of influenza in humans, further dissection of the HAsp molecule is warranted to help identify the critical structural motifs that confer enhanced virulence. This can be accomplished by performing site-directed mutational analyses of the HAsp gene and investigating the effects of these mutations on infection in the mouse model. The identification of these motifs may provide a new epidemiologic tool for surveillance of circulating animal and human influenzaviruses that could be used to predict the emergence of a new, highly virulent pandemic strain. In addition, these detailed molecular studies could facilitate the identification of antigenic epitopes to include in vaccines in order to protect people against related pandemic strains." "

The above comments are in reference to a recent article in Nature titled Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus. This is exciting and excellent work which opens the way for more fundamental basic science animal research as well as clinical studies.

Friday, December 3, 2004

Pennsylvania Has Its First Influenza Case

Type A-Fujian influenza has been confirmed in a Philadelphia resident, the first laboratory-confirmed case of influenza in Pennsylvania. Of note, this strain was included in the vaccine.

Saturday, November 27, 2004

Bird Flu Pandemic inevitable, 7 million people could die, WHO

Bird Flu Pandemic inevitable, 7 million people could die, WHO:

""The World Health Organization is urging countries to prepare for an ‘inevitable flu pandemic' it believes will probably come from a mutated bird flu virus. Dr Klaus Stohr, WHO Influenza Program Coordinator, says as many as seven million people could be killed.

Stohr is urging health ministries in Asian countries to prepare and take measures for a probable flu pandemic. Dr Stohr insists it is only a matter of time - we have gone beyond wondering whether there will be one, the stage now is trying to forecast ‘when' a pandemic will hit.

Dr Stohr says the next pandemic will most likely come from a mutation of the bird (avian) flu virus. He said "Even with the best-case scenarios, the most optimistic scenarios, the pandemic will cause a public health emergency. There are estimates which would put the number of deaths in the range of between two and seven million."

The H5N1 bird flu strain, the most dangerous, has hit Thailand and Vietnam hard. Millions of poultry have had to be destroyed - 30 people have died.

The virus only kills humans who have close contact with infected poultry. The concern among health experts is that the virus could mutate and spread from human to human. If the virus were to infect a pig, the jump (mutation) from pig to human would be much more likely (emphasis mine).

If the strain were to mutate and have the ability to spread among humans, nobody would be immune - the consequences could be catastrophic. According to Stohr, this could happen at any time.

WHO experts say that countries in Asia which have the weakest health systems are precisely the ones that need the most support as they are the most likely places to host the beginnings of a pandemic. ""

That bolded phrase--The concern among health experts is that the virus could mutate and spread from human to human. If the virus were to infect a pig, the jump (mutation) from pig to human would be much more likely--deserves further explanation. I'm reading the book The Great Influenza, by John M. Barry, who gives a nice summary of why pigs can make it fly (so to speak):

""The virus may also adapt indirectly, through an intermediary. Some virologists theorize that pigs provide a perfect "mixing bowl", because the sialic-acid receptors on their cells can bind to both bird and human viruses. Whenever an avian virus infects swine at the same time at the same time that a human virus does, reassortment of the two viruses can occur. An an entirely new virus can emerge that can infect man. In 1918 veterinarians noted oubreaks of influenza in pigs and other mammals, and pigs to day still get influenza from direct descendents of the 1918 virus. But it is not clear whether pigs caught the disease form man or man caught it from pigs.""

For more information, see The World Health Organization page on pandemic preparedness.

Friday, November 26, 2004

Making The Flu Vaccine Go Further

NEJM: Dose Sparing with Intradermal Injection of Influenza Vaccine (free full text)

NEJM: Serum Antibody Responses after Intradermal Vaccination against Influenza (free full text)

Wednesday, November 17, 2004

Do you have the flu, or something else?

Many people complain they're down with the 'flu' without really knowing whether it's influenza or not. While browsing my new Google ad sense banner (see left lower gutter) , I found a link to QuickVue, a test for influenza which I never knew existed (or had forgotten existed). It uses a nasal swab (and obtaining a sample is therefore less noxious than getting a Rapidstrep test) and takes about ten minutes to give a result. I have no information on cost.

Thursday, November 11, 2004

Flu Vaccine Shortage A Blessing In Disguise?

The flu vaccine shortage of 2004 has focused national (if not world) attention on how we produce influenza vaccines, which companies produce them, and how vulnerable our present system is to interuptions. We haven't seen a major flu pandemic like those of 1918 or 1957 or 1968 yet. It's quite possible that changes to the system that result from the current shortage will make us more prepared for the next pandemic, whenever it comes. We may be seeing the early stages of it in Thailand and Vietnam in the form of bird flu....

Weathering the Influenza Vaccine Crisis

NEJM: Weathering the Influenza Vaccine Crisis

""Influenza vaccine is especially vulnerable to interruptions in supply, because of the unique features of influenza-vaccine production. Unlike any other vaccine, influenza vaccine must be reformulated to keep pace with antigenic changes in the hemagglutinin and neuraminidase proteins of influenzaviruses — essentially necessitating the manufacture of a brand new product from scratch every year. The process is a long one, beginning with the identification of new antigenic variants in the autumn of the previous year and the selection of the strains for inclusion in the vaccine, and proceeding to the generation of appropriate reference reagents, the production and purification of the vaccine antigens, and packaging and distribution, all within a period of six to eight months.""

Thursday, November 4, 2004

Changing Shot Technique May Extend Flu Vaccine (Los Angeles Times)

Changing Shot Technique May Extend Flu Vaccine (Los Angeles Times):

""Los Angeles Times - Supplies of the influenza vaccine could be expanded by up to five times by changing how the shot is given — administering a small dose under the skin rather than a larger dose into muscle, two teams of researchers reported Wednesday.""

[Via Yahoo! News: Top Stories]

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