HEALTH 2/27-3/5/10 Bird, Other Flu Weekly Thread:Widespread Tamiflu Resistance in Japan

Link to last weeks thread:

2/19-2/26/10 Bird, Other Flu Weekly Thread:WHO H1N1 Vaccine Target Selection Failure

http://www.timebomb2000.com/vb/showthread.php?t=355281


Please See:

Confirmed cases of Swine Flu and maps
http://www.timebomb2000.com/vb/showthread.php?t=330689

Comprehensive Flu Thread, Latest reports, States, Countries, Closings.

http://www.timebomb2000.com/vb/showthread.php?t=330395

Useful Links:

Avian Influenza (Bird Flu)
http://www.cdc.gov/flu/avian/gen-info/facts.htm

Johns Hopkins on influenza:
http://www.iom.edu/Object.File/Master/33/450/Rashid Chotani.pdf

National Avian Influenza Surveillance Information:
http://wildlifedisease.nbii.gov/ai/

CDC
http://www.cdc.gov/flu/avian/index.htm

WHO
http://www.who.int/csr/disease/avian_influenza/en/index.html

CIDRAP
http://www.cidrap.umn.edu/

Official U.S. Government Web site
http://www.pandemicflu.gov/

FAO
http://www.fao.org/ag/againfo/subjects/en/health/diseases-cards/special_avian.html

Public Health Agency of Canada
http://www.phac-aspc.gc.ca/influenza/avian_qa_e.html

European Union
http://ec.europa.eu/dgs/health_consumer/dyna/influenza/country_en.htm

The World Bank
http://web.worldbank.org/WBSITE/EXT...68427~piPK:64168435~theSitePK:1793593,00.html

Widespread and Common Tamiflu Resistance in Japan
​

http://www.recombinomics.com/News/02261001/H274Y_Japan_Wide.html

The Japan NIID released sequences (at GISAID) from 13 recent isolates in Japan which were collected between November, 2009 and January, 2010. Ten of the thirteen were Tamiflu resistant because of H274Y. The geographic locations were diverse and the sequences fell onto multiple branches of a phylogenetic tree indicating they were independently introduced, while those clustered were also transmitting. The independent introductions and transmission were reported previously, but not at this high frequency of 77% (10/13).

Although A/Wakayama-C/1/2010 represents the first reported sequence from a 2010 isolate with H274Y, the large number of such sequences in December collections suggests H274Y is currently widespread in Japan. Earlier sequences created a trend of an increasing frequency of reported sequences with H274Y, but the latest report suggests that the trend is quickly moving toward fixing H274Y in pandemic H1N1, as was seen in seasonal flu.

H274Y produces resistance in Tamiflu as well as Peramivir, which leaves Relenza as the only approved antiviral unaffected by H274Y or S31N in M2. The recent reports of increased H1N1 activity on Region 4, as well as increased absenteeism in schools, raise concerns of a new wave of H1N1. Each of the prior pandemics last century had a winter/spring wave which followed a fall wave, and the emerging pandemic displaced the existing influenza A seasonal flu. The latest week flu report by the CDC (week 7) had no detection of seasonal H1N1 or H3N2, supporting a repeat of patterns seen in the past three pandemics.

The trend of increasing frequencies of H274Y in isolates in Japan, coupled with reports of low reactor recombinants, raises concerns that the winter/spring wave will be more difficult to manage.

Bird flu kills Vietnam woman​

http://www.straitstimes.com/BreakingNews/SEAsia/Story/STIStory_495735.html

HANOI - A VIETNAMESE woman who slaughtered and processed sick poultry has died from bird flu, the first fatality from the avian influenza virus this year in Vietnam, the Health Ministry said.

The 38-year-old woman died on Tuesday in a hospital in the southern Mekong Delta province of Dong Thap after fighting the H5N1 virus for 10 days, the ministry said in a statement seen on Saturday.

She is Vietnam's second human infection reported this year and the first to have died from bird flu, which thrives best in cold weather and during the peak time of bird transportation, such as this month's Tet festival to mark the Lunar New Year.

Earlier this month a three-year-old girl in the central province of Khanh Hoa recovered from bird flu, the Health Ministry said. Vietnam has confirmed 114 human infections of the H5N1 virus since 2003, 58 of them fatal, the ministry said.

It is the second highest toll after Indonesia's 134 deaths among the 15 countries on bird flu world map drawn by the World Health Organization.

Experts fear that the virus might mutate into a form easily passed from human to human, sparking a pandemic which could kill millions. -- REUTERS

Japan-made drug proves effective against avian flu in mice test ​

http://www.japantoday.com/category/...oves-effective-against-avian-flu-in-mice-test

TOKYO —

A new drug developed in Japan and now under government screening has been proven effective in tests on mice against a deadly H5N1 strain of avian influenza as well as another H5N1 strain resistant to the widely used treatment Tamiflu, according to a U.S. science publication released Friday.

A team led by Yoshihiro Kawaoka, professor of the University of Tokyo’s Institute of Medical Science, infected mice with the deadly strain and found that 70-90% of the mice given the drug, codenamed CS-8958, survived within a three-week observation period, according to the PLoS Pathogens publication.

Those without any dose of the drug, made by Daiichi Sankyo Co, died within 11 days, according to the researchers.

The team said mice infected with the Tamiflu-resistant strain and administered with CS-8958 had a higher survival rate than those given Tamiflu.

The drug is the first treatment developed in Japan from the research stage, according to Daiichi Sankyo, which aims to start marketing it in fiscal 2010. The drug maker said Feb. 1 it applied for health ministry approval for manufacture and sale.

H1N1 H274Y Tamiflu Resistance in Italian Recombinant
​

http://www.recombinomics.com/News/02281001/H274Y_Italy.html

Azienda Ospedaliero Universitaria Pisana has release a partial NA sequences from a recently treated immune-suppressed patient. The sequence, A/Italy/Pisa254/2010, has a mixed signal for H274Y. The January 26, 2010 collection is the most recent H274Y positive sequence to date and there are five additional recent synonymous acquisitions. The first two are found in four isolates from Jiangyin (see list here) indicating they were acquired via recombination. The mixed signal for H274Y also supports the presence of a mixture with H274Y selected by the treatment. In immune-suppressed patients, monitoring is more active, and the likelihood of resistant strains producing clinical problems is increased because of a compromised immune system.

The release of this sequence follows the release of 13 recent sequences from Japan. 10 had H274Y, including a January, 2010 collection. The increased detection of H274Y in the limited number of 2010 sequences raises concerns that Tamiflu resistance, like D225G/N, is on the rise.

These markers move around via recombination, which allows for jumping from one genetic background to another. In the Italian NA sequence there fist polymorphism matched the two polymorphisms in China, which provide another example of recombination. These examples are difficult to explain by the “random mutation” paradigm of WHO and collaborators. The H274Y in the above isolate is on yet another genetic background, adding further support for recombination. D225G/N has also been found on multiple genetic backgrounds, in addition to concentration in one sub-clade found largely, in Ukraine and Russia.

These increasing frequencies of H274Y and D225G/N raise concerns that as a new wave develops, new variants will arise with D225G/N and H274Y.

The increasing reports of H274Y in 2010 isolates add to those concerns.

Animal Disease Warning Issued as Bird Flu Kills Mekong Resident ​

http://www.dowell-netherlands.com/2010/02/animal-disease-warning-issued-as-bird.html

The Vietnamese Ministry of Health reported the first human bird flu death this year on Friday, prompting an animal health official to warn that animal health diseases could sweep the country in 2010.

The 38-year-old victim from the Mekong Delta Tien Giang Province was killed February 23, soon before Pasteur Institute in Ho Chi Minh City confirmed she had tested positive with the H5N1 virus.

The victim’s name has not been released. She had killed and processed sick chicken before getting sick on February 13.The victim was hospitalized eight days after that at Sa Dec Hospital in the nearby Dong Thap Province when her condition became worse.

She was diagnosed with severe viral pneumonia. Also on Friday, Hoang Van Nam, acting head of the Animal Health Department at the Ministry of Agriculture and Rural Development, said bird flu outbreaks have been reported in Nam Dinh and Dien Bien Provinces in the north, Khanh Hoa in the central region, and Ca Mau and Soc Trang in the Mekong Delta.

Gov't heightens bird flu monitoring ​

http://english.yonhapnews.co.kr/news/2010/02/26/0200000000AEN20100226002300320.HTML

SEOUL, Feb. 26 (Yonhap) -- The government said on Friday it is seeking to enhance monitoring and decontamination measures across South Korea to prevent outbreaks of avian influenza as migratory birds start arriving in the country.

The Ministry for Food, Agriculture, Forestry and Fisheries said recent outbreaks of the highly pathogenic avian influenza (HPAI) in Southeast Asia have raised the need to warn poultry farmers of possible dangers in the coming weeks.

Sloppy Surveillance Raises H1N1 Pandemic Concerns​

http://www.recombinomics.com/News/03021003/H1N1_Sloppy.html

Hospital surveillance of severe acute respiratory infection (SARI): During week 07/2010, 19 SARI cases were reported. Of the 11 influenza viruses isolated from SARI patients and subtyped, four were the 2009 pandemic A(H1N1) virus.

Virus type/subtype Number of cases during current week

Influenza A 11

A (pandemic H1N1) 4

A(subtyping not performed) 4

A(H3)

A(H1) 3

A(H5)

Influenza B

Unknown 8

The above comments and data are from the ECDC week 7 report, which demonstrates the sorry state of pandemic surveillance in Europe. In the past three pandemics, a fall wave has been followed by a winter/spring wave. A winter/spring wave would begin about now, but week 7 reports are incomplete and may have entry errors. Although there were only 19 patients listed, virus was not isolated in 8. Of the 11 isolates, sub-typing was not performed on 4. On the remaining seven all were H1N1, but 3 were said to be seasonal H1N1 at a time when seasonal H1N1 has all but disappeared. Thus, it is unclear if almost half the 7 H1N1 sub-typed were actually seasonal H1N1, or were pandemic H1N1 that were mis-reported or entered in the wrong field.

Week 7 is a critical time period. The fall wave has ended and a new wave should be forming, based on the pattern of the last 3 pandemics. However, surveillance has only identified 19 patients, all of whom are likely infected with pandemic H1N1, yet pandemic H1N1 was only confirmed in four.

Moreover, 5 of 17 are said to have received the pandemic vaccine (the status of 2 was unknown), raising concerns that vaccine failure in Europe is widespread. The frequency in the 17 severe cases with reported vaccination status is similar to the vaccination rate of the entire population, suggesting that the vaccine has little effect on the emerging virus.

The number of reported cases is low, but the low number is linked to poor surveillance. Most H1N1 infected patients are either not tested or tested with a rapid test which has a sensitivity which is notoriously low and even lower for H1N1 (the CDC has reported levels as low as 10%). This low sensitivity is due in part to the ability of pandemic H1N1 to quickly move to the lungs. More serious cases would be in ICU’s where collection of appropriate lung fluids would be easier and more likely to yield H1N1 virus. However, more than half of these severe cases have not yielded virus or were not sub-typed.

Thus, at a time when surveillance should be increased, the poor surveillance yields low numbers which mitigates interpretation of the alarming numbers which suggest the frequency of vaccinated patients in the H1N1 severe group is similar to the frequency in the population as a whole.

Indonesia Says Bird Flu Is Under Control; Expert Disagrees​

http://www.thejakartaglobe.com/home/indonesia-says-bird-flu-is-under-control-expert-disagrees/361893

The government is claiming success in its efforts to tackle avian flu despite almost half of all the deaths recorded around the world occurring in Indonesia.

Bayu Krisnamurthi, executive chairman of the National Committee for Avian Influenza Control and Pandemic Influenza Preparedness (Komnas FBPI), told the Jakarta Globe on Wednesday that although Indonesia was leading the world in the number of recorded fatalities from bird flu, “the total number of reported cases keeps decreasing.”

Since the virus first emerged in 2003, 138 people have died from infections in Indonesia, while the worldwide death toll is less than 300. In 2006 alone, more than 40 Indonesians succumbed to the H5N1 virus.

In 2009, however, there were just 13 confirmed deaths from bird flu, the lowest number of fatalities since 2005. “The virus is still sometimes found in poultry and occasionally in humans, but now people already know how to react and respond to the problems,” Bayu said.

He said the improved awareness was proof that the campaigns promoted by the government were working well, and that people were learning about how to prevent transmission and what to do in the event of an outbreak.

Bayu said that in a bid to better integrate programs relating to animal diseases that could be jump to humans, also known by the technical term zoonosis, Komnas FBPI’s would be replaced when its mandate expired on March 13 with a National Committee on Zoonosis (Komnas Zoonosis).

“What we really need now is a stronger position to be able to not only make recommendations, but also act on those recommendations,” he said, adding that the finer details, such as the new body’s budget, were yet to be worked out.

Meanwhile, Chairul Anwar Nidom, a virologist with the Tropical Disease Center at Airlangga University in Surabaya, said the government’s claims of success in controlling bird flu were premature.

“It depends on how you define the word success,” he said. “If it means we have made progress, then yes, we are quite successful, but if it means bird flu in Indonesia is totally under control, then no, we’re still far from being successful.”

Nidom said that even though the number of human fatalities had declined in 2009, the virus remained endemic in poultry across the country.

“As long as the virus is still here, it still has the possibility to infect humans at any time,” he said.

Nidom said bird flu persisted in the nation partly because the government’s programs designed to combat its spread were disorganized and inefficient.

“Each ministry works independently, while they should be working together,” he said.

“Bird flu is a very complex issue because it affects both the health and economic sectors.”

According to Nidom, Komnas FBPI’s successor should be granted more wide-ranging powers to make policy and directly implement it in the field.

More northern provinces see bird flu outbreaks​

http://english.vovnews.vn/Home/More-northern-provinces-see-bird-flu-outbreaks/20103/113166.vov

Bird flu has hit another 2 northern provinces-Tuyen Quang and Ha Giang-announced by the Veterinary Department under the Ministry of Agriculture and Rural Development (MARD) on March 3.

The disease was confirmed in a flock of poultry raised by a family in Cap Tien commune, Son Duong district, Tuyen Quang province on February 26.

On the previous day, an outbreak of bird flu occurred on two family poultry farms in Nguyen Trai commune, Ha Giang province. As of March 1, the total number of poultry found to be infected with the disease in these two households was up to 100 heads of chicken. Most of them died.

Now, health care agencies are coordinating with local authorities to proactively carry out measures to prevent and curb the spread of the disease.

At present, the disease has spread to 7 provinces nationwide. Ca Mau, Dien Bien, Soc Trang, Nam Dinh and Khanh Hoa have not yet passed the 21-day deadline without any new outbreak.

In addition, an outbreak of foot-and-mouth disease is occurring in four provinces-Nghe An, Dien Bien, Tien Giang and Son La.

Association of D225G/N With Severe H1N1 Cases In Norway
​

http://www.recombinomics.com/News/03041001/D225GN_Norway.html

Here we report the occurrence of an amino acid substitution, aspartic acid to glycine in position 222 (D222G) in the HA1 subunit of the viral haemagglutinin, in clinical specimens from 11 out of 61 cases analysed in Norway with severe outcome. Such mutants were not observed in any of 205 mild cases investigated (Table), thus the frequency of this mutation was significantly higher in severe (including fatal) cases (p<0.001, Fisher’s exact test, two-sided) than in mild cases. D222G mutants were detected throughout the sampling period, from the first recorded severe cases in July until early December. The frequency of another substitution in the same position, D222E, did not differ significantly between mild and severe cases (p=0.772). Yet another substitution, D222N, was observed in a very few cases (n=4), and at a higher rate than expected among severe cases (three of four cases, p=0.039). The wild type 222D was, not surprisingly, significantly less frequent in severe than in mild cases (p<0.001).

In several of the patients where D222G mutant viruses were found, they coexisted with wildtype 222D viruses. Further analysis of this phenomenon is ongoing.

The above comments from a report from Norway in Eurosurveillance confirm that D225G/N (H3 numbering) is significantly more common in severe cases in Norway. These data support sequences released by Mill Hill from fatal cases in Ukraine, as well as fatal cases in Russia, which raises concerns that a third wave with a higher frequency of D225G/N would produce a higher incidence of severe and fatal cases. This concern is increased by the designation of a Ukraine isolate with D225G as a low reactor.

The levels of D225G/N in severe and fatal cases in Norway, Ukraine, and Russia are in marked contrast to D225E, which is common in several western European countries, including UK, Spain, and Italy, which discounts the possibility that these position 225 polymorphisms are due to copy errors. Instead, the multiple genetic backgrounds that are shared with wild type sequences strongly supports movement of D225G by recombination. D225G has also been found with low reactor polymorphisms in Russia and Italy.

The above report also supports the common finding of D225G as a mixture, either with wild type, D225N, or both.

Avian influenza - situation in Egypt - update 31​

http://www.who.int/csr/don/2010_03_04/en/index.html

4 March 2010 -- The Ministry of Health of Egypt has announced five new cases of human H5N1 avian influenza infection.

The first case is a 53 year-old male from Shobra Elkhima district, Qaliobia Governorate. He developed symptoms on 27 February and was hospitalized on 27 February, where he received oseltamivir treatment. He is in a critical condition.

The second case is a 1 year-old male from Banha district, Qaliobia Governorate. He developed symptoms on 22 February and was hospitalized on 23 February, where he received oseltamivir treatment. He is in a stable condition.

The third case is a 10 year-old male from Meet Ghamr district, Dakalia Governorate. He developed symptoms on 10 February and was hospitalized on 14 February, where he received oseltamivir treatment. He is in a moderate condition.

The fourth case is a 30 year-old female from Kellin District, Kafr El-Sheik Governorate. She developed symptoms on 10 February and was hospitalized on 11 February, where she received oseltamivir treatment. She is in stable condition.

The fifth case is a 13 year-old male from Kafr El-Sheik District, Kafr El-Sheik Governorate. He developed symptoms on 10 February and was hospitalized on 14 February where he received oseltamivir treatment. He is in stable condition.

Investigations into the source of infection indicated that the five cases had exposure to sick and dead poultry.

The cases were confirmed by the Egyptian Central Public Health Laboratories, a National Influenza Center of the WHO Global Influenza Surveillance Network (GISN).

Of the 104 laboratory confirmed cases of Avian influenza A(H5N1) reported in Egypt, 30 have been fatal.

Avian influenza – situation in Viet Nam - update 8​

http://www.who.int/csr/don/2010_03_04a/en/index.html

4 March 2010 -- The Ministry of Health has reported three new confirmed cases of human infection with the H5N1 avian influenza virus, including one fatality. Two cases have been confirmed at the National Institute of Hygiene and Epidemiology (NIHE) and one case has been confirmed at the Pasteur Institute, Ho Chi Minh City.

The first case is a 3 year-old female residing in Ninh Hoa District, Khanh Hoa Province. She developed symptoms on 27 January 2010, and was hospitalized at Ninh Hoa district hospital on 28 January. She is recovering well. The source of exposure is currently under investigation. Her family raises chickens but did not report any mass poultry illness or death. However, Ninh Hoa District and Van Ninh District are currently being monitored because of recent H5N1 poultry outbreaks.

The second case was a 38 year-old female residing in Cai Be District, Tien Giang Province. She developed symptoms on 13 February 2010. The patient was admitted to the Sa Dec Hospital in Dong Thap Province on 21 February where she died on 23 February. An epidemiological investigation showed that the patient had slaughtered and processed sick water fowl.

The third case is a 17 year-old female residing in Son Duong District, Tuyen Quang Province. She developed symptoms on 19 February 2010 and was taken to the Son Duong District General Hospital on 24 February where she is currently being treated for mild breathing difficulties. Approximately, 10 days ago, there were unexplained deaths of chicken in the patient's household. She participated in the disposal of the dead poultry.

Of the 115 cases confirmed to date in Viet Nam, 58 have been fatal.

Link to next weeks thread:

3/6-3/14/10 Bird&Other Flu Weekly Thread:Norway H1N1 D225G/N Refutes WHO Position

http://www.timebomb2000.com/vb/showthread.php?p=3666348#post3666348