H1N1 STRAIN RESISTANT TO ANTIVIRALS (Thailand)

HenryN · #1 August 8th, 2009, 05:55 PM

Health experts are urging the public to stay calm after the first case of a Thai H1N1 flu patient developing resistance to the main drug prescribed to treat the virus was found.
The discovery of a H1N1 strain which is resistant to the antiviral drug oseltamivir was made in laboratory tests at Ramathibodi Hospital. Virus experts and health authorities will meet tomorrow to review the national strategy on tackling H1N1 flu in the wake of the find.
The meeting will discuss the need to reassess treatment guidelines, and stockpile the alternative antiviral drug zanamivir, said Deputy Public Health Minister Manit Nopamornbodee.
The discovery comes as the Public Health Ministry has extended its distribution of oseltamivir to clinics across the country. This will lead to the drug being prescribed more, possibly further increasing the risk of resistance growing.
Heath experts have cautioned that overuse of the antiviral drug may lead to drug resistance. Mr Manit called on the public not to panic.
"The discovery of a drug-resistant strain is common. We have told clinics to be careful when prescribing the drug," he said. Prof Dr Wasun Chantratita, chief of virology and molecular microbiology at Ramathibodi Hospital, said the drug-resistant strain was found in a Thai who had since recovered from H1N1.
He said another case of antiviral resistance had been recorded in a seasonal-flu patient. The discovery of the two cases of drug resistance was made in laboratory testing of 50 samples of confirmed type A H1N1 virus.
Of 15,000 samples sent for testing, 10,000 were confirmed as influenza and of those 80% were the A H1N1 strain. "We can say anyone who contracts influenza now can be assumed as having H1N1," he said. "Interestingly, we have never found any patient who contracts H1N1 and seasonal flu at the same time."
About 80% of seasonal flu patients are drug-resistant, so the chances of H1N1 patients being resistant were also very high.
"But prescription of the antiviral drug is needed to reduce fatalities. As long as an antiviral vaccine is not yet available, it is necessary to use the drug," he said.
Dr Thawee Chotpitiyasunont, chairman of a committee setting national health strategy on the flu pandemic, said monitoring of drug resistance must be stepped up.

http://www.bangkokpost.com/news/loca...-to-antivirals

HenryN · #2 August 8th, 2009, 06:05 PM

Quote:

Originally Posted by niman

Health experts are urging the public to stay calm after the first case of a Thai H1N1 flu patient developing resistance to the main drug prescribed to treat the virus was found.
The discovery of a H1N1 strain which is resistant to the antiviral drug oseltamivir was made in laboratory tests at Ramathibodi Hospital. http://www.bangkokpost.com/news/loca...-to-antivirals

The above comments do not address Tamiflu treatment in this patient. Previously all reported resistance cases linked to Tamiflu treatment were in patients receiving a prophylatic does. The dose used to treat this patient is unclear and the report does not state when or if the patient was treated with Tamiflu.

AlaskaDenise · #3 August 8th, 2009, 06:44 PM

Quote:

Interestingly, we have never found any patient who contracts H1N1 and seasonal flu at the same time."

Is that easily distinguishable?

If a person had dual exposure, can one strain be so virulent it would immediately out-compete the other or is there a residual evidence of both?

I'm just surprised that in 10,000 samples there were no dual infections, yet 20% of all infections were non-novel H1N1.

.

HenryN · #4 August 8th, 2009, 07:09 PM

Quote:

Originally Posted by AlaskaDenise

Is that easily distinguishable?

If a person had dual exposure, can one strain be so virulent it would immediately out-compete the other or is there a residual evidence of both?

I'm just surprised that in 10,000 samples there were no dual infections, yet 20% of all infections were non-novel H1N1.

.

This report doesn't add up. The level of H274Y in Brisbane H1N1 should be close to 100%, but the report mentions 1 such sequence (seasonal), which may indicate that the number of sequenced isolates is very low (so the number of isolates with H274Y may be much more than 1).

Similarly, it sounds like the discovery was through routine testing / sequencing, suggesting the patient was NOT on prophylatic Tamiflu. Since the patient has already recovered, it may be a mild case and may not involve Tamiflu treatment.

HenryN · #5 August 8th, 2009, 07:37 PM

Commentary

AlaskaDenise · #6 August 8th, 2009, 07:58 PM

Quote:

Originally Posted by niman

Commentary

Commentary

Tamiflu Resistant Pandemic H1N1 in Thailand
Recombinomics Commentary 00:25
August 9, 2009

Health experts are urging the public to stay calm after the first case of a Thai H1N1 flu patient developing resistance to the main drug prescribed to treat the virus was found.

The discovery of a H1N1 strain which is resistant to the antiviral drug oseltamivir was made in laboratory tests at Ramathibodi Hospital.

The above description describes the first reported case of oseltamivir (Tamiflu) in a pandemic H1N1 patient in Thailand. The report follows the release of a sequence from Hunan, China with H274Y, which followed the release of a sequence from a patient in Singapore, which followed the release of the sequence with H274Y from a patient in Demark. All three sequences were distinct from each other, as well as previous sequences from Japan (Osaka and Yamaguchi) and Hong Kong. Moreover, H274Y has been reported in sequences from patients in Quebec and Tokushima.

The recent release of the sequences signals global spread of resistance, but the report from Thailand creates additional concerns. The number of lab confirmed cases in Thailand should now be above 10,000 and the number of lab confirmed fatalities likely tops 100 (see details in map links). The confirmed cases and deaths have been on a sharp upward slope and the contribution of the resistance to the large number of deaths is unclear.

Similarly, the report does not indicate the treatment status of the patient, who recovered. Previously, most of the described patients were identified while on prophylactic Tamiflu. Thus, development of symptoms while on Tamiflu led to the isolate and sequencing or the reported isolates. However, the resistance in the Thai patient was identified during routine screening raising concerns that the patient was not treated with Tamifu.

The prior isolate from Hong Kong was from a patient traveling from San Francisco who had a mild case and did not receive Tamiflu, before or after she tested positive. Similarly, the sequences from Singapore and Hunan were quietly released at GISAID or Genbank, raising concerns that the resistance was identified during routine sequencing, since the samples were collected in May and mid June, but not reported until this week.

These latest results signal global spread of Tamiflu resistance, which may be associated with evolutionarily fit pandemic H1N1.

Details on the circumstances associated with the resistant patients in Singapore, Hunan, China, and Thailand would be useful.

.

ironorehopper · #7 August 9th, 2009, 03:50 AM

Quote:

Originally Posted by AlaskaDenise

Is that easily distinguishable?

If a person had dual exposure, can one strain be so virulent it would immediately out-compete the other or is there a residual evidence of both?

I'm just surprised that in 10,000 samples there were no dual infections, yet 20% of all infections were non-novel H1N1.

.

France detected a co-infection between H1N1 2009 and seasonal strain. Cfr. the Eurosurveillance report on Sci Library: http://www.flutrackers.com/forum/sho...d.php?t=117414

AlaskaDenise · #8 August 9th, 2009, 04:02 AM

Quote:

Originally Posted by ironorehopper

France detected a co-infection between H1N1 2009 and seasonal strain. Cfr. the Eurosurveillance report on Sci Library: http://www.flutrackers.com/forum/sho...d.php?t=117414

In your referenced llnk, they reported that out of 358 positives tests, there was one co-infection.

If that same ratio held in Thailand, there could have been 22 co-infections.
(using 8000 positive H1N1 tests)

.

HenryN · #9 August 9th, 2009, 09:48 AM

BANGKOK, 9 August 2009 (NNT) – The Ministry of Public Health has warned patients to take all 10 Oseltamivir pills for 5 consecutive days as prescribed by physicians in order to prevent drug resistance and further spread of the H1N1 virus.

Upon the report of resistance against Oseltamivir detected at Ramathibodi Hospital, Public Health Ministry Spokesperson MD Suphan Srithamma admitted its high possibility, adding that the drug being used on a large number of patients could also lead to a higher chance of resistance.

The spokesperson assured that the ministry had been very cautious in its drug prescription, elaborating that Oseltamivir was only given to patients with severe symptoms. He said the medication was most effective within 48 to 72 hours after the first indication of flu symptoms.

MD Suphan added that all people worldwide had an equal opportunity to be infected with the H1N1 flu as the majority still had no immunity against the virus. He also estimated that at present there were about 300,000 to 500,000 people in Thailand with sufficient immunity against the infection.

http://thainews.prd.go.th/en/news.php?id=255208090039

HenryN · #10 August 9th, 2009, 09:49 AM

Academics: No need to panic over resistance against Oseltamivir

BANGKOK, 9 August 2009 (NNT) – Academics have confirmed no need to panic over the discovery of the H1N1 virus’s resistance against Oseltamivir, assuring that experts will convene to discuss laboratory information tomorrow.

Following a recent news report of H1N1 patients’ resistance against Oseltamivir, virologist MD Prasert Thongcharoen, as Chairperson of the Advisory Subcommittee on Medicine and Public Health, stated that he had not received an official report on the matter yet. He expected the issue to be brought up during the meeting of experts tomorrow while urging the public not to panic over the information.

MD Prasert cited that the resistance rate of the virus against Oseltamivir in Thailand was low compared to the statistics in Japan. He added that drug resistance had been found in Hong Kong, Denmark and Canada as well. He, however, admitted that this issue must be confirmed with test results from the laboratories of Chulalongkorn and Siriraj Hospitals.

Meanwhile, an expert of the Medical Services Department, MD Tawee Chotpitayasunondh, stated that resistance against Oseltamivir was not beyond expectation, but it must be considered by the number of cases. He insisted that there was no need to panic, and the treatment policy would remain the same.

	News ID: 255208090040
	Reporter : Santibhap Ussavasodhi News Date : 09 August 2009 http://thainews.prd.go.th/en/news.php?id=255208090040

HenryN · #11 August 9th, 2009, 10:34 AM

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http://thaiinsider.info/2009news/the.../3357-----2009

bcgauspohl · #12 August 9th, 2009, 11:42 AM

Dr. Niman,

I've been reading your commentaries and posts about H1N1 developing Tamiflu resistance in more and more locations around the globe. My question is have you heard anything about H1N1 resistant cases popping up in Vietnam? Has anyone on this site heard of H1N1 resistance showing up in Vietnam? I ask because I saw a news story a few days back about it but I haven't heard anything since. I don't know if these H1N1 resistant cases were officially confirmed by the Vietnamese government. This is the news article published on Thursday July 30th:

Vietnamese H1N1 flu shows sign of resistance to treatments

VietNam News
Publication Date: 30-07-2009

At least four A /H1N1 flu patients had not responded normally to treatment at the HCM City Tropical Diseases Hospital, its deputy director said on Monday.

Two of the cases might be drug resistant, said Dr Tran Tinh Hien.

The announcement by Hien came as the city stepped up preparations to fight the spread of the flu, assigning more facilities and manpower as the number of patients testing positive for the virus increased sharply in recent days.

Health officials have warned that up to 2 million people could be infected by the virus as the epidemic spreads.

Dr Phan Van Nghiem, head of the HCM City Department of Health’s Medical Profession Division, said the municipal administration had allocated VND6 billion for the purchase of facilities like ambulances, respiratory aids and masks for city hospital staff.

All hospitals in the city were now allowed to receive and treat A/H1N1 flu patients and an additional 300 beds hadbeen prepared at district-level hospitals, health officials said during a meeting of health officials and the city’s Committee for Epidemic Prevention on Monday.

Besides the hospital facilities, medicines to treat the flu were also a major issue mentioned by doctors.

With the predicted number of patients, the city needs around 20 million tablets of Tamiflu, while it currently has just 13,000 in stock.

The Ministry of Health would be asked to assist the city in getting more tablets. A city health department official said it had requested the ministry for an immediate addition of 30,000 Tamiflu tablets.

Truong Quoc Cuong, head of the Viet Nam Drug Administration, said the country had enough materials to produce 10 million Tamiflu tablets. If necessary, more medicines as well as materials would be imported, he said.

Meanwhile, director of the Ha Noi Health Department Le Anh Tuan said that the city had prepared an A/H1N1 prevention plan.

Four sub-committees have been formed based on the scenario that health staff, medical facilities and drugs were reserved to provide treatment for 2,000 patients. All hospitals have reserved special isolation and treatment areas and have strengthened communication, and examination and monitoring for the disease.

The municipal health department also requested all State offices and schools to inform the local health sector or to call the department hotline if a case of A/H1N1 occurs. The health sector will send staff to localise and isolate patients, and monitor the disease area.

According to the department’s statistics, as of Tuesday there were 47 A/H1N1 cases in the city. Thirty-one had been discharged from the hospital and 16 were being treated at the National Institute of Infectious and Tropical Diseases.

The Hai Phong Health Department Tuesday also reported the first A/H1N1 flu cluster in the city when five members of one family were found positive with the virus in Kenh Duong Ward, Le Chan District.

The Ministry of Health reported 31 new A/H1N1 cases, bringing the nation’s total to 703 cases and still no fatalities.

http://www.asianewsnet.net/news.php?id=7090&sec=14&t=

bcgauspohl

wotan · #13 August 9th, 2009, 11:43 AM

Welcome bcgauspohl!

HenryN · #14 August 9th, 2009, 11:47 AM

Quote:

Originally Posted by bcgauspohl

Dr. Niman,

I've been reading your commentaries and posts about H1N1 developing Tamiflu resistance in more and more locations around the globe. My question is have you heard anything about H1N1 resistant cases popping up in Vietnam? Has anyone on this site heard of H1N1 resistance showing up in Vietnam? I ask because I saw a news story a few days back about it but I haven't heard anything since. I don't know if these H1N1 resistant cases were officially confirmed by the Vietnamese government. This is the news article published on Thursday July 30th:

Vietnamese H1N1 flu shows sign of resistance to treatments

VietNam News
Publication Date: 30-07-2009

At least four A /H1N1 flu patients had not responded normally to treatment at the HCM City Tropical Diseases Hospital, its deputy director said on Monday.

Two of the cases might be drug resistant, said Dr Tran Tinh Hien.

The announcement by Hien came as the city stepped up preparations to fight the spread of the flu, assigning more facilities and manpower as the number of patients testing positive for the virus increased sharply in recent days.

Health officials have warned that up to 2 million people could be infected by the virus as the epidemic spreads.

Dr Phan Van Nghiem, head of the HCM City Department of Health’s Medical Profession Division, said the municipal administration had allocated VND6 billion for the purchase of facilities like ambulances, respiratory aids and masks for city hospital staff.

All hospitals in the city were now allowed to receive and treat A/H1N1 flu patients and an additional 300 beds hadbeen prepared at district-level hospitals, health officials said during a meeting of health officials and the city’s Committee for Epidemic Prevention on Monday.

Besides the hospital facilities, medicines to treat the flu were also a major issue mentioned by doctors.

With the predicted number of patients, the city needs around 20 million tablets of Tamiflu, while it currently has just 13,000 in stock.

The Ministry of Health would be asked to assist the city in getting more tablets. A city health department official said it had requested the ministry for an immediate addition of 30,000 Tamiflu tablets.

Truong Quoc Cuong, head of the Viet Nam Drug Administration, said the country had enough materials to produce 10 million Tamiflu tablets. If necessary, more medicines as well as materials would be imported, he said.

Meanwhile, director of the Ha Noi Health Department Le Anh Tuan said that the city had prepared an A/H1N1 prevention plan.

Four sub-committees have been formed based on the scenario that health staff, medical facilities and drugs were reserved to provide treatment for 2,000 patients. All hospitals have reserved special isolation and treatment areas and have strengthened communication, and examination and monitoring for the disease.

The municipal health department also requested all State offices and schools to inform the local health sector or to call the department hotline if a case of A/H1N1 occurs. The health sector will send staff to localise and isolate patients, and monitor the disease area.

According to the department’s statistics, as of Tuesday there were 47 A/H1N1 cases in the city. Thirty-one had been discharged from the hospital and 16 were being treated at the National Institute of Infectious and Tropical Diseases.

The Hai Phong Health Department Tuesday also reported the first A/H1N1 flu cluster in the city when five members of one family were found positive with the virus in Kenh Duong Ward, Le Chan District.

The Ministry of Health reported 31 new A/H1N1 cases, bringing the nation’s total to 703 cases and still no fatalities.

http://www.asianewsnet.net/news.php?id=7090&sec=14&t=

bcgauspohl

No, I saw those reports as well as a similar report from India, but have not seen any confirmations (isolation of the H1N1 with H274Y).

bcgauspohl · #15 August 9th, 2009, 11:49 AM

Did anyone see this news story on H1N1 cases showing possible resistance to Tamiflu treatment in Vietnam from Thursday July 30th?

http://www.asianewsnet.net/news.php?sec=14&id=7090

bcgauspohl · #16 August 9th, 2009, 11:52 AM

Dr. Niman,

Do you have a link(s) to the news report(s) about possible H1N1 resistance to Tamiflu treatment in India?

HenryN · #17 August 9th, 2009, 12:01 PM

Quote:

Originally Posted by bcgauspohl

Dr. Niman,

Do you have a link(s) to the news report(s) about possible H1N1 resistance to Tamiflu treatment in India?

It was at the same time as the first reports from Vietnam.

HenryN · #18 August 9th, 2009, 08:27 PM

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http://search.sanook.com/news/admin_...OFQyMDowODowMQ==

HenryN · #19 August 10th, 2009, 01:51 PM

Commentary

HenryN · #20 August 11th, 2009, 05:03 AM

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Khunying Ratns daughter said. Government should protect and measures should not let the disease spread to another. Because during this rainy season to start. People may begin to be sick and ill flu. The body will be unhealthy and vulnerable to infections easily. In addition, if the spread of disease. May cause such a disease and will harden to resist drug control. The consequences could cause the disease to spread in the second round. So the government should push this agenda is the National Migration is not only interested in the appointment of police

http://www.khaosod.co.th/view_news.p...MHdPQzB4TVE9PQ==

HenryN · #21 August 11th, 2009, 05:21 AM

The above translation confirms that H274Y is being indentified in H1N1 by a routine screening test, which is specific for the genetic change that encodes H274Y. However, it still remains unclear if this change was found in one swine flu patient with H274Y or if the one was in reference to one type of H1N1 (swine).

The original story said two patients, one infected with seasonal H1N1 and one infected with swine H1N1. However, H274Y is at or near 100% in Brisbane/59, which would be the strain of most seasonal flu. Thus, if a number of seasonal flu isolates were screened, there would be many examples of H274Y. Thus, the "one" may be in reference to the type of H1N1 and the story may have actually said the H274Y was found in two types of H1N1, seasonal H1N1 and swine H1N1.

Of course if "one" was in reference to the type of H1N1, then the actual number of swine H1N1 Thai isolates identified with H274Y may be significantly higher than one.

HenryN · #22 August 11th, 2009, 07:44 AM

Thai-UK import deal for nasal medication

Writer: APIRADEE TREERUTKUARKUL

Published: 11/08/2009 at 12:00 AM

Newspaper section: News

Thai authorities will import second-line type-A (H1N1) flu medicine following the case of an infected patient who did not respond to doses of oseltamivir.
Laboratory tests at Ramathibodi Hospital confirmed the discovery of a mutant flu strain that was resistant to the medicine.
Government Pharmaceutical Organisation (GPO) managing director Witit Artavatkun said the organisation would sign the agreement today to import zanamivir, the second-line anti-flu regimen, from Britain-based GlaxoSmithKline for use at state hospitals and for medicinal stockpiling to fight the flu pandemic.
"The British company has agreed to halve the price of the medicine," Dr Witit said.
Under the agreement, the price of zanamivir would be cut to 450 baht a dose.
The imported medicine will be distributed to state hospitals nationwide as a back-up for flu pandemic preparedness, he said.
Dr Witit said the GPO planned to import 30,000 doses as part of tomorrow's agreement.
As well as 50 million tablets of oseltamivir, Thailand has stockpiled 20,000 doses of zanamivir intranasal spray. The government has approved the Public Health Ministry's proposal to buy a further 20,000 more doses for stockpiling, bringing the total to 70,000. Dr Witit expressed concern over reports of the oseltamivir-resistant virus discovery because the drug resistance could affect the GPO's plan to produce the local first-line drug GPO-A-Flu.
Virologist Prasert Thongcharoen, chairman of the subcommittee responsible for academic and strategic planning against the flu pandemic, said the public should not panic about the reported drug resistance case.
"If we want to fight against invisible diseases, we should have sufficient weapons just like having both knives and guns," he said.
"Stockpiling the anti-flu drugs for 10% of the population is not even considered high."
Dr Prasert said the viral resistance case needed further tests to confirm whether the virus was resistant to oseltamivir.
The case was proved only by a sequencing test designed to monitor a residue of neuraminidase protein in H1N1 virus sample.
However, it is essential to test the virus resistance on the specific drug to confirm the resistance, he said.
In Thailand, only laboratories at Siriraj Hospital and the Department of Medical Sciences could conduct such a test.
Only Denmark, Hong Kong, Canada and Japan have reported oseltamivir-resistance cases, according to the World Health Organisation.
The members of the subcommittee from medical schools are drafting regulations and guidelines for using each anti-flu regimen for treatment to avoid the problem of drug resistance, Dr Prasert said.

http://www.bangkokpost.com/news/loca...lu-drug-influx