Many of the resistant cases involved people with severely weakened immunity, reinforcing the importance of monitoring for the problem in such patients, the WHO said in today’s issue of its Weekly Epidemiological Record.

The 225 cases come from 20 countries and include 65 cases in the Americas, 77 in Europe, 1 in Africa, and 82 in the Western Pacific region, the agency said. All the isolates had the H275Y mutation that confers resistance to oseltamivir but not to the other neuraminidase inhibitor in general use, zanamivir (Relenza).

Of 142 cases for which data were available, 56 (40%) were in severely immunocompromised patients, and 54 (38%) were linked to treatment of flu. Another 16 cases (11%) were associated with preventive treatment, and 16 others did not involve any known antiviral use.

The WHO reviewed reports of three clusters of resistant cases, one each in the United States, the United Kingdom, and Vietnam. They involved:

Four severely immunocompromised patients in the same ward at Duke University Hospital in Durham, N.C., in October and November; in three cases, resistance was found before the drug was used
Eight patients with hematological malignancies at the University Hospital of Wales in Cardiff, Wales, in November, at least four of whom contracted the resistant virus from someone else
Seven healthy young adults in Vietnam who traveled together by train last July and were believed to have caught the virus from an unidentified index case; the cluster apparently did not lead to any further cases
The WHO said the number of resistant cases remains low despite the large scale of the pandemic, the wide use of oseltamivir, and extensive monitoring.

“Although there is no evidence of general community circulation of such resistant viruses, there is clear evidence of limited person-to-person transmission in several epidemiological settings,” the agency said. It added that active surveillance for resistant cases should continue and all cases should be investigated and reported to health authorities.

Children are especially vulnerable to swine flu, also known as H1N1. The disease struck three boys who attended a two-week boys’ camp in July 2009. They were given medication and sent home, according to the report.

For 10 days, campers and counselors who lived in adjoining cabins took a drug called oseltamivir (Tamiflu) with an eye toward preventing infection.

“Alcohol-based hand sanitizer was provided at each of the daily activities, in the boys’ cabins and in the dining hall, and counselors were educated by the medical staff on the spread of influenza and its prevention through good hand hygiene,” the authors wrote. “All cabins, bathrooms and community sports equipment were sprayed or wiped down with disinfectant each day.”

No one else at the camp became ill or tested positive for swine flu after they got home. However, 78 percent of the staff and counselors and 31 percent of the campers suffered from one or more side effects — including nausea, vomiting and headache — from the preventive medication. But they didn’t stop taking it.

“You will normally kill off the bacteria or viruses that are sensitive to our drugs over a period of time those bacteria or viruses will adapt and the ones that are left are totally resistant to the antibiotic,” says Rick Kilgore with Clinical Research Consultants.

The problem is doctors are prescribing Tamiflu for H1N1 and no studies have been conducted to determine what effect Tamiflu has on H1N1. Researchers are not sure if doctors are prescribing the correct dose to completely kill the virus. The current dose may be killing the majority of the virus but what is left over becomes resistant.

“We could end up with a pretty serious situation where we don’t have any anti-virals that the H1N1 will respond to that is why it is critical to determine what the appropriate dosing and the length of dosing is,” says Kilgore.

Starting next week, 100 researchers nationwide will begin a study. A Hoover company Clinical Research Consultants is one of them. It will take 400 people with H1N1 and give them different doses of Tamiflu for either five or ten days.

“They will have a home visit almost daily from us to get throat swabs and nasal swabs to document if the virus is shedding or if they still have virus in the body,” says Kilgore.

Results could be released as soon as December.

Boston-law law firm Ropes and Gray is one company that made arrangements for hundreds of its employees and their families to obtain the antiviral medicine Tamiflu to protect them from swine flu.

They say it’s to protect their staff, but some doctors say it could hurt the public. Dr. Steven Esrick, the Medical Director of the Valley Medical Group told 22News that stockpiling happens because Tamiflu is most effective if it’s taken within 48 hours.

But, he said “the problem is if a lot of people take it when they don’t need it, it will increase the resistance and make it useless.”

It could also make Tamiflu unavailable for those who need it the most. Serio’s Pharmacy in Northampton said they have Tamiflu for people who have prescriptions for it.

But, Owner Paul Serio said that many of those who stockpile Tamiflu, buy it illegally online. He said this can be unsafe because people “don’t know where the product is coming from or if the product is, in fact, the product that you ordered.”

According to Joanne Levin, the Infection Prevention Physician at Cooley Dickinson Hospital, there are already sporadic cases of Tamiflu resistance to H1N1.

So it’s extremely important that people only take it if they are given a prescription from their doctor.

President Viktor Yushchenko wrote to the United States, the European Union, NATO and Ukraine’s neighbours to ask for drugs and equipment to fight the spread of the A(H1N1) virus, according to a statement released by his office.

“The threat weighing on Ukraine’s national security which we cannot fight alone forces me to ask our close friends and strategic partners for urgent help,” Yushchenko wrote. Ukraine has also ordered 16 tonnes of antiviral drug Tamiflu from Switzerland, the president’s office said.

The health ministry said 60 people had died from respiratory problems in the past week, without indicating how many had succumbed to H1N1.

The former Soviet republic has so far reported four fatalities from more than 190,000 cases of swine flu, with nearly 8,000 needing hospital treatment.

Poland and Slovakia responded to Yushchenko’s appeal on Sunday night, sending protective masks and supplies of Tamiflu. Swine flu has become a political issue in Ukraine as the country gears up for January’s presidential election.

Both Yushchenko and his rival, Prime Minister Yulia Tymoshenko, have tried to take the lead in managing the crisis prompted by the epidemic.

The Danish patient, who has since recovered, was taking the drug as a prevention to avoid the contraction of swine flu, Reddy said. He was probably already infected with the virus, and resistance to the drug emerged because he was given the lower prevention dose.

This is a case of so-called drug-induced resistance, which is rare, but it was known from clinical studies that this can happen, Reddy said. Around 0.4% of adults, and around 4% of children, were shown to develop resistance to Tamiflu in clinical studies, he said. Drug-induced resistance occurs when a patient who is taking the drug develops resistance. It differs from naturally incurring resistance, where a virus strain in itself isn’t responding to the drug. This had been the case with the winter flu virus that was spreading in Europe in 2008, he added.

This isn’t the case here, meaning that Tamiflu is still working against swine flu, and Roche thus expects the World Health Organization to continue to back the use of the drug, Reddy said. Over the last five years governments around the world have invested significant amounts of money to build emergency stockpiles of Tamiflu and Relenza, a similar drug produced by U.K.-based GlaxoSmithKline Plc (GSK).

Roche sales and profits have been greatly affected, skyrocketing for a while when the stockbuilding started, then falling off sharply when inventories were filled. This first surge in demand for Tamiflu came after a new bird flu virus had emerged in Asia, and had been widely expected to be the cause of the first pandemic in more than 40 years. That didn’t happen though because the virus never was circulated heavily in humans. Instead the now circulating swine flu virus emerged in Mexico a few months ago, causing the 21st centuries first pandemic.

The U.S. alone has a stockpile of 50 million courses of antiviral medicine on a federal level and a further 22 million courses on a state level. Governments are holding the drugs to protect people working on the front line of a pandemic, such as healthcare workers, thereby limiting the spread.

At some point, there will certainly be resistance to Tamiflu, said Birgit Kulhoff, pharmaceutical analyst in Zurich with private bank Rahn & Bodmer.

“Sooner or later there will be resistance, and I would expect that to happen when the swine flu virus starts mixing with seasonal flu viruses,” she said. As such, an isolated case in Denmark doesn’t yet change the sales prospects of Tamiflu. “It would have been much more worrisome if we saw repeated cases of resistance in the Southern hemisphere, where it’s winter now, and the viruses could mix,” she said.

Roche shares closed up CHF2, or 1.3%, at CHF148.60, in a higher Swiss market. The European healthcare sector overall was 0.8% higher.

The Health Sciences Authority (HSA) approves 20 to 30 such applications yearly, including an extension for the anti-viral drug Tamiflu.

Roche, the manufacturer of the drug, had asked that two more years be added to the five-year shelf-life of the drug in July last year. The HSA okayed the application after checks against the manufacturer’s data to ensure that the drug would be as potent as ever.

Even with an extension to seven years, the potency levels of Tamiflu were found to be between 90 per cent and 105 per cent, said Dr Lim Poh Lian, senior consultant at the Communicable Diseases Centre (CDC).

‘As a clinician, there is no way I will be giving medication to my patients if I knew it was ineffective,’ she said.

She was responding to doctors who had misgivings about the extended shelf-life of the drug, intended to combat those with the H1N1 flu.

Roche has specified that all stocks have to be stored at below 25 deg C and kept in a dry place with a humidity level of about 60 per cent. The Health Ministry said that the Government’s Tamiflu stockpile is stored in an air-conditioned environment, where temperatures and humidity levels are monitored hourly.

Ministry officials were also asked about Tamiflu meant for commercial supply, which had its shelf-life similarly extended on June 18 this year. Did they meet quality conditions as well given that there could be temperature changes in storage?

The ministry said that Roche had also provided data at higher temperatures of 30 deg C for 36 months and 40 deg C for six months ‘which will address the issues on short-term temperature spikes that occur’.

Dr Lee Yik Voon, a general practitioner in Circuit Road who had previously worked in a pharmaceutical company, said it was common for drug companies to test the efficacy of a drug often to see if its shelf-life could be extended.

Those conditions include being pregnant, being under age 5 and having chronic medical conditions, such as asthma and diabetes.

But the free pills won’t be available right away. The state health department and the state’s 12 local health departments have yet to work out the details, such as whether the drugs will be distributed through the government or at hospitals. Utah received 25 percent of its share of the Strategic National Stockpile of antivirals in April — 87,000 doses, adding to the 55,000 it already had on hand.

There has been hesitancy to use the stockpile during the H1N1 outbreak because private pharmacies can order the drugs. And, public health officials want the stockpile available in the fall and winter, when they fear the now-mild flu could morph into something more virulent. The fact that the stockpile will be released now “suggests the illness in Utah seems to be a little more robust than in other parts of the country,” said Gary Edwards, executive director of the Salt Lake Valley Health Department.

And, he said, “we recognize there are members of our community who are at high risk who don’t have insurance or other ways to pay for the [$90] medication.”

The Utah Hospitals and Health Systems Association requested that the stockpile be released for the uninsured. The association’s Debra Wynkoop said hospitals are seeing and diagnosing the uninsured, but have no way to treat them.

“We give them a prescription to go fill and they’re coming back to the hospital even sicker because they didn’t fill the prescription. They didn’t have the money,” she said. It will be up to a doctor to decide whether a prescription is warranted, according to the state health department. While some doctors have been waiting for a confirmed flu test to write a prescription, those tests have a high false negative rate and the state has urged doctors to use their clinical judgment. If people exhibit flu-like symptoms, they likely have H1N1.

The new policy won’t help Patricia Ravera, who e-mailed The Salt Lake Tribune to ask where she can get treatment because she is uninsured. Her daughters, who are covered by Medicaid, were diagnosed with the flu and got Tamiflu. But Ravera and her brother couldn’t find a low-income clinic that is accepting new patients to get diagnosed. They both had fevers and were vomiting. She said she was bounced around between their health department and her children’s doctor.

Ravera, of Provo, doesn’t have an underlying health condition that would qualify her for the free drugs. She has stayed home to limit the spread.

“Of course I have frustration with the system,” she wrote in Spanish. “Nobody is worried for us.”
The picture is different for the insured.

Glen Worthington, of East Millcreek, said his family easily got prescriptions for Tamiflu two days after his 7-year-old daughter came down with flu-like symptoms this week. His wife has asthma, but neither he nor his daughter have underlying risk factors and they still got treated.

“Let’s just attack it,” was the doctor’s attitude, said Worthington, who has insurance.

The region now has 51 confirmed cases, 16 of which were reported in within 48 hours.

Regional health authorities are confirming on Friday morning, that it’s likely the drug will be restricted to only the severely sick, as the number of swine flu cases sky-rockets.

Health Minister Tony Ryall, is expected to make a announcement regarding Tamiflu distribution later on Friday morning.

Regional Public Health medical officer Stephen Palmer says as testing centres succumbed to the volume of work it was no longer possible to distribute Tamiflu with the same freedom as during the initial outbreak.

“Only so many tests can be done in one day. If people are unwell they should stay home,” he says.”Only those with severe symptoms or serious health conditions will be given Tamiflu.”

Meanwhile, a national support line has been set up, to help GPs struggling to cope with the rising numbers of people, fearing they have swine flu.

The helpline will provide GPs with support for any questions they have, and give up-to-date information on the swine flu situation.

The move comes, as the Ministry of Health begins a change in strategy, to manage the outbreak, rather than contain it.

The number of confirmed cases of swine flu around the country has now risen to 153.

A 17-year-old boy from the school’s disabled unit has swine flu, but his 49 contacts have not being advised by the South Australian Government to stay in home quarantine. The principal of Pasadena High School, Dean Low, says the Health Department gave the students Tamiflu because they were considered to be in the vulnerable category.

He says the decision not to quarantine students will be widely welcomed.

“It’s a pretty big disruption to your program to have to do that, this was a lot of work as it was,” he said.

“But it’s meant that all of these students are able to continue their education program without any problems. “They’re students with intellectual disability, the Health Department treated them as special, you know they’re a special unit so I think they got extra precautions rather than what would normally happen so I think that was a really good thing.”

Positive results

Meanwhile, the principal of Kidman Park Primary School, which sent 130 students home on Monday because of the swine flu, says the situation has actually produced some positive results.

Principal John Clarke says parents are being more cautious, with many choosing to keep children home voluntarily. “In our eyes, we think although not good to have had the human swine flu, it has made our parents aware and certainly people are making sure they’re following precautions and so on,” he said.

The Health Minister, John Hill, announced a change in policy on Wednesday, telling Parliament schools will no longer be advised to shut down if they have swine flu cases.