WHO - Comparing deaths from pandemic and seasonal influenza

22 DECEMBER 2009 GENEVA -- Efforts to assess the severity of the H1N1 influenza pandemic sometimes compare numbers of confirmed deaths with those estimated for seasonal influenza, either nationally or worldwide. Such comparisons are not reliable for several reasons and can be misleading.

Numbers of deaths for seasonal influenza are estimates. They use statistical models designed to calculate so-called excess mortality that occurs during the period when influenza viruses are circulating widely in a given population.

Estimates using all-cause mortality
The models use data, as recorded in death certificates and medical records, indicating mortality from all causes, and compare the number of deaths during epidemics of seasonal influenza with baseline data on deaths during the rest of the year. The assumption is that infections with influenza viruses contribute to the “excess mortality” observed during the influenza season.
During epidemics of seasonal influenza, around 90% of deaths occur in the frail elderly, who often suffer from one or more chronic medical conditions. Although influenza can worsen these conditions and contribute to death, testing for influenza viruses is not done in most cases, and deaths are usually attributed to an underlying medical condition.

Methods for estimating excess mortality were introduced in the 19th century to capture these influenza-associated deaths that would otherwise be missed. Such estimates have helped counter assumptions that influenza is a mild illness that rarely kills.

Laboratory-confirmed deaths
In contrast, numbers of deaths from pandemic influenza, as notified by national authorities and tabulated by WHO, are laboratory-confirmed deaths, not estimates. For several reasons, these numbers do not give a true picture of mortality during the pandemic, which is unquestionably higher than indicated by laboratory-confirmed cases.

As pandemic influenza mimics the signs and symptoms of many common infectious diseases, doctors often do not suspect H1N1 infection and do not test. This is especially true in developing countries, where deaths from respiratory diseases, including pneumonia, are common occurrences. Moreover, routine testing for pandemic influenza is costly and demanding, and beyond the reach of most countries.

When testing confirms H1N1 infection in patients with underlying medical conditions, many doctors record these deaths as due to the medical condition, and not to the pandemic virus. These cases are also missed in official statistics.

As recent studies have shown, some tests for H1N1 infection are not entirely reliable, and false-negative results are a frequent problem. Accurate test results further depend on how and when samples were taken. Even in the best-equipped hospitals, doctors have reported seeing patients with distinctive and virtually identical disease profiles, yet only some have positive test results.
Moreover, in a large number of developing countries, systems for vital registration are either weak or non-existent, meaning that most deaths are neither investigated nor certified in terms of the cause.

Younger age groups
Comparisons of deaths from pandemic and seasonal influenza do not accurately measure the impact of the pandemic for another reason. Compared with seasonal influenza, the H1N1 virus affects a much younger age group in all categories – those most frequently infected, hospitalized, requiring intensive care, and dying.

WHO continues to assess the impact of the influenza pandemic as moderate. Accurate assessments of mortality and mortality rates will likely be possible only one to two years after the pandemic has peaked, and will rely on methods similar to those used to calculate excess mortality during seasonal influenza epidemics.

Source: http://www.who.int/csr/disease/swineflu/notes/briefing_20091222/en/index.html

New antiviral compound (still undergoing trials) said to be more effective than Tamiflu

A study in the Dec. 21 edition of the Proceedings of the National Academy of Sciences suggests that a new compound may be more potent and safer for treating H5N1 influenza than the antiviral oseltamivir (trade name Tamiflu). The new compound, called T-705, is effective in mice even up to 3 days after infection. This means T-705 may be effective in people who have already entered a disease state. It is also effective against circulating seasonal influenza viruses, as evidenced by human testing in Japan, where the compound is on the brink of Phase III clinical trials in humans. Clinical trails will further test the efficacy and safety of T-705 in humans.

T-705 is considered safer and more effective than oseltamivir because it targets viral polymerase, an enzyme specific to viruses that allows them to make copies of their genetic material (RNA). Once polymerase is disabled, the virus can no longer make new viral particles, thus ending the chain of infection.

Source: http://www.eurekalert.org/pub_releases/2009-12/uow-cft121709.php
PNAS: http://www.pnas.org/

Egypt reports 90th confirmed case of H5N1

WHO:

21 December 2009 -- The Ministry of Health of Egypt has reported a new laboratory confirmed human case of avian influenza A(H5N1) on 19 December 2009.

The case is a 21 year old female from the El Tanta District of Gharbia Governorate. She developed symptoms of fever and cough on 15 December 2009.

She was admitted to Tanta Fever Hospital where she received oseltamivir treatment on the same day. She is in a stable condition. Investigation revealed that the case had close contact with dead poultry and was involved in slaughtering sick birds.

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

Of the 90 laboratory confirmed cases of Avian influenza A(H5N1) reported in Egypt, 27 have been fatal.


Source: http://www.who.int/csr/don/2009_12_21/en/index.html

WHO confirms human H5N1 case in Cambodia

18 December 2009 -- The Ministry of Health of Cambodia has announced a new confirmed case of human infection with the H5N1 avian influenza virus.

The 57-year-old male, from Ponhea Kreak District, Kampong Cham Province, developed symptoms on 11 December. The case was admitted to Kampong Cham Provincial Hospital on 16 December, where he received treatment. He is in a stable condition. The presence of the H5N1 virus was confirmed by the National Influenza Centre, the Institut Pasteur du Cambodge. A team led by the Ministry of Health is conducting field investigations into the source of his infection.

Of the 9 cases confirmed to date in Cambodia, 7 have been fatal. This is the first diagnosed case in Cambodia during 2009.

Source: http://www.who.int/csr/don/2009_12_18/en/index.html

Molecule Linked to Severe H1N1

Below is an article from the Globe and Mail by Carly Weeks (referenced from Crawford Kilian at Crofsblog):

Published on Tuesday, Dec. 15, 2009 5:56PM EST

One of the scariest aspects of the H1N1 pandemic is the apparent randomness of the virus: While most people who contract it recover from symptoms after several days, pockets of people are hit with extremely severe, and sometimes deadly, illness.

Now, it appears scientists are one step closer to understanding why some people may be at greater risk of developing virulent forms of H1N1, as well as other respiratory illnesses.

Toronto scientists, in collaboration with colleagues from Spain, have identified a molecule they believe is linked to severe forms of illness. The results, published in the December issue of the journal Critical Care, could eventually help health officials target populations that may be most vulnerable, they said.

“It's probably not an isolated example that is specific for H1N1, and it probably spills over to other types of respiratory illness,” said David Kelvin, senior scientist and head of the experimental therapeutics division at the Toronto General Research Institute and one of the study's authors. The researchers looked at blood samples from 10 H1N1-infected individuals in intensive-care units, 10 patients in non-ICU parts of the hospital, 15 outpatients with the illness and 15 people without H1N1. They focused on analyzing 29 cytokines, or molecules that regulate immune function, to determine if there were any patterns among those with severe forms of the disease.

They discovered that those patients with the most virulent forms had elevated levels of one particular molecule called interleukin 17. High levels of the molecule have previously been associated with inflammation and autoimmune diseases, Dr. Kelvin said.

It's too early to draw a link between high levels of that molecule and the risk of pneumonia or death related to H1N1, he said.

It is still not known if elevated levels of the molecule can predict severe illness, or whether it applies to large groups of people. But the finding does give scientists a solid basis to work with as they continue in their quest to identify what makes certain people more vulnerable to virulent respiratory illness.

Dr. Kelvin said he and his colleagues have been searching for this kind of discovery for years, and they believe it has implications for targeting preventive therapy in future pandemics, as well as seasonal influenza. While they have looked in the past at patients with other respiratory illnesses, they never found a meaningful connection between severe illness and elevated molecule levels.

“This is the first time we've come across something in 10 years, and we've looked pretty rigorously,” Dr. Kelvin said. “It's almost like a smoking gun. If you don't know where to look you'll never get the job done.”

Dr. Kelvin said researchers are expanding their study to look for similar patterns in people living in other countries, such as China. They hope to find links between molecule levels and severe illness, and will look for genetic differences that may make some more susceptible to severe illness.

Eventually, health officials may be able to develop a simple blood test that can identify who is at greatest risk of severe illness in future pandemics or flu outbreaks.

Dr. Kelvin said the work could have major implications for developing countries, which often can't afford comprehensive inoculation campaigns to protect their populations.

WHO to Begin Sending H1N1 Vaccine to Developing Countries

Article from the Associated Press, December 17, 2009

The World Health Organization plans to start shipping 2009 H1N1 vaccine to Azerbaijan, Afghanistan and Mongolia in the next few weeks, flu chief Keiji Fukuda said Thursday.

Another 32 developing countries are in line to get the vaccine soon. The U.N. health agency has prioritized sending the shots to northern hemisphere countries first, which are being hit harder by swine flu than countries in the southern hemisphere.

The agency had hoped to send the vaccine earlier, but the effort has been delayed by manufacturing problems and bureaucracy.

When WHO declared swine flu to be a pandemic, or global outbreak, in June, it warned the virus could have a devastating impact in countries across Africa with high numbers of people with health problems like malnutrition, AIDS, and malaria. Most people who catch swine flu only have mild symptoms like a fever or cough and recover without needing medical treatment.

WHO has a stockpile of about 180 million swine flu shots, donated by six drug makers and a dozen countries.

Countries hoping to get swine flu vaccine from WHO must meet three conditions. They have to formally ask for it, agree to certain terms and conditions on how it will be used, and develop a national plan to make sure the right people — like health workers and those with underlying health problems — get it first. WHO is hoping to send enough swine flu vaccine to cover about 10 percent of populations in poor countries.

Countries likely won't start vaccinating their populations until a few weeks after they receive the vaccine, but Fukuda said it wasn't too late to ship the vaccine — even though swine flu appears to have peaked in several northern hemisphere countries, like Britain and the U.S.

"This is a virus that we don't expect to suddenly disappear," Fukuda said, adding WHO expected the virus to keep circulating for the next few years.

Fukuda said it was "premature" to consider whether the pandemic might be on the decline, and that WHO would consult experts before making such a declaration. He said flu activity this year had peaked "extraordinarily early" and warned there were still several months of winter to come.

Source: http://www.google.com/hostednews/ap/article/ALeqM5i-Qd-q3ALSGUV0tZqwFVoy1GlGfQD9CL35LG1

Also, please see a detailed Vaccine Deployment Update by WHO at http://www.who.int/csr/disease/swineflu/vaccines/h1n1_vaccination_deployment_update_20091217.pdf

Thailand Confirms First Case of Human-to-Pig 2009 H1N1 Influenza

Today, Thailand confirmed its first case of a pig infected with H1N1 contracted from humans, senior officials said. Below are some excerpts from an AsiaOne article describing the incident.

Agriculture minister Thira Wongsamut said that one of 80 pigs in a sample group tested for the virus at Kasertsart University farm in the central province of Sara Buri had contracted 2009 H1N1 influenza.

The ministry has quarantined a five kilometer radius around the farm, where university research is carried out, as a precautionary measure. Also, officials say that new health checks will be conducted at the farm every three days.

The ministry's permanent secretary Yukol Limlamthong said that none of the 132 workers at the university farm had contracted swine flu. He could not confirm if a research student had brought the virus in.

"We can not prove that, but the test results show the pig contracted the virus from a human," Yukol said.

Thira [stressed] that as mentioned before, eating pork did not pose a danger.

"The virus has spread from human to pigs in several countries. [But] we've had no case of it spreading from pigs to humans," he said.

Since the swine flu outbreak began in April, the ministry said it has tested more than 26,000 pigs for the virus and has confirmed 29,741 human cases of the flu and 190 of those were fatal.

The Thai government has a one-million dollar fund set aside to combat swine flu.

Source: AsiaOne News http://news.asiaone.com/News/Latest%2BNews/Health/Story/A1Story20091217-186509.html

Germany and Spain Seek to Cut H1N1 Vaccine Orders

As reported earlier, the German Ministry of Health has been faced with a situation in which the country has excess vaccine for 2009 H1N1 due to weak demand within the country. Now, in addition to Germany, Spain has expressed a desire to return unused vaccine to the pharmaceutical companies according to a report on the specialist news service APM Health Europe.

A health ministry official in Madrid said Spain expected to either return surplus vaccines to suppliers so they could be sold at pharmacies, or send them to other European Union countries to help with their vaccination programs.

The World Health Organization's (WHO) flu expert Keiji Fukuda said countries with surplus vaccine had "a number of options" including donating it to those who have none, or keeping it in reserve for a later date.

"This is a virus that we don't expect to just suddenly disappear," he told a briefing.

WHO is coordinating efforts to encourage rich countries to share vaccines with poorer nations who had little or no access to supplies. Fukuda said six manufacturers and 12 countries had so far pledged some 180 million doses of vaccines to be distributed to around 95 countries.

Source: Reuters http://www.reuters.com/article/idUSTRE5BG2PD20091217

Non-Safety-Related Voluntary Recall of Sanofi Pasteur H1N1 Pediatric Vaccine

As part of its quality assurance program, Sanofi Pasteur, performs routine, ongoing stability testing of its 2009 H1N1 vaccine after the vaccine has been shipped to providers. Stability testing measures the strength/potency of a vaccine over time. It is performed because sometimes the strength of a vaccine can go down over time. On December 7, Sanofi Pasteur notified CDC and FDA that the potency in one batch (also called a “lot”) of pediatric syringes that had been distributed was later found to have dropped below a pre-specified limit. As a result of this finding, Sanofi Pasteur tested additional lots and found that three other lots that had been distributed also had an antigen content that, while properly filled at the time of manufacturing, was later measured to be below pre-specified limits. A total of 800,000 vaccines have been recalled.

There are no safety concerns with these lots of H1N1 vaccine. All lots successfully passed pre-release testing for purity, potency and safety. Infants and children who received vaccines from these lots do not need to be revaccinated because the vaccine potency is only slightly below the “specified” range. The vaccine in these lots is still expected to be effective in stimulating a protective response despite this slight reduction in the concentration of antigen. However, as is recommended for all 2009 H1N1 vaccines, all children less than 10 years old should get the recommended two doses of H1N1 vaccine approximately a month apart for the optimal immune response. Therefore, children less than 10 years old who have only received one dose of vaccine thus far should still receive a second dose of 2009 H1N1 vaccine.

Parents of children who received vaccine from the recalled lots do not need to take any action, other than to complete the two-dose immunization series if not already completed. Sanofi Pasteur will send providers directions for returning any unused vaccine from these lots.

Source: CDC http://www.cdc.gov/h1n1flu/vaccination/syringes_qa.htm

Prolonged Shedding of 2009 H1N1 Influenza Virus

A recent study published in the journal, Eurosurveillance, discusses two case reports from France, in which two patients exhibited prolonged shedding of the virus 14 and 28 days after the onset of symptoms. The patients did not have immunodepression and were treated with neuraminidase inhibitors. This prolonged shedding was not associated with the emergence of the resistance mutation H275Y in that has been recorded in some cases.

Viral shedding of seasonal influenza A viruses was initially estimated to occur over a period between five and seven days. In humans experimentally infected with the 2009 H1N1 influenza virus, oseltamivir administration shortened the median duration of viral shedding from 107 to 58 hours. Prolonged shedding of seasonal influenza viruses has been demonstrated in immunocompromised patients even when treated with antiviral drugs, potentially leading to the emergence of viral resistant mutations. Similarly, most patients with pandemic H1N1 influenza infection may be shedding virus from one day before the onset of symptoms until five to seven days after the onset of symptoms. For infections with the pandemic influenza A(H1N1)v virus, prolonged viral shedding has been reported in immunocompromised patients treated with oseltamivir, in association with emergence of viral resistance to the drug.

This could have implications in regards to the spread of the disease. There is not yet a clear pattern on which groups of individuals may shed longer than others, and further studies are need to investigate this.

Source: Eurosurveillance http://eurosurveillance.org/ViewArticle.aspx?ArticleId=19434

On Wednesday, December 9th, The New England Journal of Medicine published an article on a community cluster of oseltamivir-resistant 2009 H1N1 influenza in Vietnam. The article summarizes community level transmission of the resistant virus among students riding a train from Ho Chi Minh City to Hanoi.

Excerpts from the NEJM article - LQ Mai et al.:

“Oseltamivir-resistant infection with the 2009 pandemic influenza A (H1N1) virus has so far been described only rarely… Only 3 of the 32 patients with oseltamivir-resistant infection reported on as of this writing were not receiving oseltamivir when the resistant viruses were detected, and ongoing community transmission has not yet been shown. However, the emergence of oseltamivir-resistant 2009 H1N1 influenza remains a grave concern, since widespread oseltamivir resistance has been observed in seasonal H1N1. This resistance was unrelated to selective drug pressure, and the H275Y substitution did not appear to reduce transmissibility or severity. We report on a cluster of seven cases of oseltamivir-resistant 2009 H1N1 infection in Vietnam.

In July 2009, during a 42-hour journey, 10 students socialized together in the same train carriage. None of the students knew each other before the journey, none had contact with a person with suspected influenza in the week before the trip, none were symptomatic during the journey, and none were previously or currently receiving oseltamivir. Fever developed in four of the students within 12 hours after arrival and in two more students within 48 hours after arrival.
Nasal swabs, throat swabs, or both from all seven persons were positive for 2009 H1N1 RNA when tested with reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays, and viruses were successfully cultured from specimens obtained from three of the persons. The H275Y substitution was detected retrospectively in diagnostic specimens obtained from all seven subjects before any oseltamivir treatment.

All patients recovered uneventfully, although one patient, with the highest 50% inhibitory concentration, continued to test positive on RT-PCR until day 9, despite receiving oseltamivir from the day of the onset of illness.

In this cluster, infection developed in at least 6 of the 10 people who were probably exposed to the index patient; this shows that resistant 2009 H1N1 viruses are transmissible and can replicate and cause illness in healthy people in the absence of selective drug pressure. Ongoing transmission from the cluster was not detected, but the tracing of all contacts was not possible, so ongoing transmission cannot be ruled out. However, only three other resistant cases have been detected in Vietnam as of this writing, and all were due to selection of resistant viruses during treatment rather than person-to-person transmission.

The loss of oseltamivir as a treatment option for severe 2009 H1N1 infection could have profound consequences.”

Recommendations to minimize risk included the following:

• The use of oseltamivir should be restricted to prophylaxis and treatment in high-risk persons or the treatment of people with severe or deteriorating illness.
• Antiviral stockpiles should be diversified.
• Optimal dosages and combination therapies should be urgently studied.
• Close monitoring and reporting of resistance to neuraminidase inhibitors.

This transmission episode is notable, as it is one of the largest clusters of oseltamivir-resistant 2009 H1N1 cases recorded thus far, with the highest number of epidemiologically-linked cases occurring among previously health people who were not taking the antiviral.

Helen Branswell from The Canadian Press reported on WHO’s reaction to the publication of the community cluster.

Excerpts:

“…The event is a warning that resistant viruses can spread among healthy people and more such events may be in store, an antiviral expert with the World Health Organization said.

‘What this looks to be is ... the sort of situation we have been alert for, because it's something that we certainly don't want to see happening but need to know about if it does,’ Charles Penn said in an interview from Geneva.

Penn said this event is different from two recent clusters, in which severely immunocompromised patients in hospitals in Wales and North Carolina developed and probably transmitted among themselves Tamiflu-resistant H1N1 virus. It's known that resistance develops easily in such patients.

Prior to this report, he said, there have only been four cases spotted in people who hadn't taken the drug and didn't have traceable exposure to someone who had.

‘And then the risk of this sort of event occurring is going to increase with more virus around and those infections being treated.’ "

http://content.nejm.org/cgi/content/full/NEJMc0910448

http://www.winnipegfreepress.com/canada/breakingnews/78906557.html

CDC: Updated Interim Recommendations for the Use of Antiviral Medications in the Treatment 2009 H1N1

The CDC has posted updated recommendations on their website for clinical treatment of 2009 H1N1. Below are some highlights from the document.

Who to treat

Prompt empiric treatment is recommended for persons with suspected or confirmed influenza and:

• Illness requiring hospitalization
• Progressive, severe, or complicated illness, regardless of previous health status, and/or
• Patients at risk for severe disease (see below for groups at high risk)

How to treat

• Antiviral drugs: oseltamivir (oral), zanamivir (inhaled)
• Initiate treatment as early as possible after onset of symptoms
• Treat empirically before diagnostic test results are reported
• When definitive diagnosis is indicated, request definitive diagnostic tests (rRT-PCR*, viral culture) rather than rapid tests (RIDT*, DFA*)

Clinical Assessment

While most persons who have had confirmed or suspected 2009 H1N1 influenza have had a mild, uncomplicated self-limited respiratory illness similar to typical seasonal influenza and while persons not considered to be at increased risk of developing severe or complicated illness may not require treatment, they can be considered for antiviral treatment. Benefits of treating such patients might include a reduced duration of illness. However, based on experience with seasonal influenza treatment, patients not considered to be at increased risk of developing severe or complicated illness and who have mild, uncomplicated illness are not likely to benefit from treatment if initiated more than 48 hours after illness onset. Clinical judgment is always an essential part of treatment decisions.

People who are already recovering from influenza do not need antiviral medications for treatment. Options for close follow-up should be carefully considered. Clinicians who prefer not to treat empirically should discuss signs and symptoms of worsening illness with such patients and arrange for follow up at least by telephone.

Clinical algorithm for consideration in the assessment of persons with mild or uncomplicated influenza illness

Source: CDC http://www.cdc.gov/h1n1flu/recommendations.htm

Germany to Sell H1N1 Vaccines Abroad Due to Weak Demand

The German Ministry of Health has confirmed that the country plans to sell more than two million H1N1 vaccinations abroad due to weak domestic demand.

Only about five percent of the German public has been vaccinated, according to Health Minister Philip Roesler. He said he was checking with other countries to see if they needed any of the medicines and that Ukraine had already signaled interest. A health ministry senior official, Hartmut Schubert, said that the vaccines could even be donated and that there had been requests from Afghanistan and some other Eastern European countries.

The 2.2 million vaccinations are due to be delivered in late December. German states ordered 50 million vaccinations that are due for delivery in several phases until the spring of 2010.

Only about 5 percent of the general public and 15 percent of medical professionals in Germany have been vaccinated. Regional states in Germany started the vaccination program on October 26.

Swine flu deaths so far stand at 86 in Germany.

Source: Reuters http://www.reuters.com/article/idUSTRE5B71K720091208

Caring for Someone Sick at Home

The CDC has released updated guidance on home-based care for sick individuals. Though many hospitals and clinics may be much busier than normal due to the 2009 H1N1 pandemic, the good news is that most people with flu will be able to be cared for at home and will feel better in about a week.

The recommendations address:

• how to make and manage a sick room
• how to check for and prevent fluid loss in sick individuals
• medicine safety, especially for children
• how to treat the individual flu symptoms (cough, fever, and others)

Source: CDC http://www.cdc.gov/h1n1flu/homecare/

Egypt: Possible Nationwide School Closures

By Reem Leila

No one seems to know how severe the swine flu epidemic will be, leaving the Egyptian government scrambling to respond. Thousands of parents have been left clueless as the number of infections and fatalities increases and the Ministry of Health has announced it may close schools nationwide if cases of pneumonia and H1N1 continue to rise. The return of 73,000 Egyptian pilgrims from Saudi Arabia is increasing public anxiety. Many already doubt the end of term exams, scheduled for the end of January, will take place.

Captain Hassan Rashed, head of Cairo Airport, says each group of returning pilgrims is accompanied by two doctors to check on them. "On their arrival at the airport pilgrims are thermally scanned in groups. Anyone displaying flu-like symptoms or suffering from a fever is sent to the airport's quarantine area and from there to hospital."

Five pilgrims have died from swine flu and 73 others are reported to have contracted the virus during the hajj. None of the cases involves Egyptians.

Awad Mahgour, director of communicable diseases at the WHO, points out the level of infection is low so far given that the hajj is the largest annual gathering in the world. But Mahgour warns true levels of infection will not be clear until pilgrims return to their home countries.

A press release issued by Health Minister Hatem El-Gabali outlines plans to vaccinate the first 1.5 million of Egypt's 16 million students. "The ministry will receive 1.2 million doses of H1N1 vaccine in January, the third batch Egypt has received. Pupils at schools with the highest densities will be given priority," said El-Gabali. Cabinet Information and Decision Support Centre (IDSC) figures show that of the 3,216 cases of swine flu reported, 1,881 were in schools and 169 in universities.

As the suspension of a whole academic year to check the spread of swine flu among school children is being considered there is a growing feeling that officials responsible for measures to contain the H1N1 virus -- which so far has proved less dangerous than seasonal flu -- are overreacting.

"The H1N1 virus in its current form is weak when compared to seasonal flu, with a fatality rate in Egypt of less than one per cent," says Mohamed Awad Tageddin, professor of respiratory diseases at Ain Shams University. "Some 94 per cent of those who contracted the virus in Egypt have recovered."

Many parents are worried about losing the money they have paid for their children's school fees for the year. While private international schools provide students with daily curriculums and assignments on the Internet students at less equipped institutions have been left with no other choice than costly private classes, which are being held at homes or in non- governmental education centres, to supplement the Education Ministry's site and the six terrestrial channels that broadcast the curricula from primary one until the end of the secondary stage.

Source: Al-Ahram Weekly http://weekly.ahram.org.eg/2009/975/eg3.htm?

WHO AFRO Organizes Workshop on Vaccine Deployment to Member States

Two five-day inter-country workshops on pandemic 2009 H1N1 vaccine deployment organized by WHO for its Member States in the African Region were held in November in Abuja, Nigeria.

Both workshops aim at:

• Strengthening the capacity of countries to deploy the new H1N1 pandemic influenza vaccine and other ancillary supplies,
• Improving the ability of Member States to identify gaps and plan for the mobilization of the extra resources needed to deploy the vaccine and other ancillary supplies
• Providing countries with necessary information to update their legal frameworks to allow for the importation and use of the new vaccine and other ancillary supplies,
• Providing participants with information and familiarizing them with procedures that could impact on logistics during the deployment H1N1 vaccines, and
• Orienting participants on ways of establishing a common management body at all levels of the health system so as to ensure better coordination and effective communication between all governments and civil society sectors.

WHO has negotiated the donation of a limited number of pandemic influenza vaccines from several manufacturers and donor countries. Given that current demand outstrips supply, these donations, will help increase supplies of pandemic vaccines to populations that would otherwise not have access.

Source: http://www.afro.who.int/press/2009/pr20091119.html

WHO Use of Advisory Bodies in Responding to the Influenza Pandemic

WHO issued a statement today acknowledging rising concerns that ties with the pharmaceutical industry among experts on the Organization’s advisory bodies may influence policy decisions, especially those relating to the influenza pandemic. WHO says that these criticisms are understandable but unfounded.

The agency has stated that there are many safeguards in place within the Organization to manage possible conflicts of interest in relationships expert advisers. External experts who advise WHO are required to provide a declaration of interests that details professional or financial interests that could compromise the impartiality of their advice. Procedures are in place for identifying, investigating and assessing potential conflicts of interest, disclosing them, and taking appropriate action such as excluding an expert from participating in a meeting.

Under the provisions of the revised International Health Regulations that were passed into legal force in 2007, an Emergency Committee advises the WHO Director-General on matters such as declaring a public health emergency of international concern, the need to raise the level of pandemic alert following spread of the H1N1 virus, and the need to introduce temporary measures, such as restrictions on travel or trade. Final decisions are made by the Director-General, as guided by the Committee’s advice. All members of the Emergency Committee sign a confidentiality agreement, provide a declaration of interests, and agree to give their consultative time freely, without compensation. Members of the Committee are drawn from a roster of about 160 experts covering a range of public health areas.

WHO has expressed that public perceptions about the current H1N1 influenza pandemic, as well as national preparedness plans, were strongly influenced by a five-year close watch over the highly lethal H5N1 avian influenza virus, which was widely regarded as the virus most likely to ignite the next influenza pandemic. A pandemic caused by a virus that kills more than 60% of the people it infects is strikingly, and fortunately, very different from the reality of the current pandemic.

The brief goes on to say that adjusting public perceptions to suit a far less lethal virus has been problematic. Given the discrepancy between what was expected and what has happened, a search for ulterior motives on the part of WHO and its scientific advisers is understandable, though without justification.

Source: Pandemic (H1N1) 2009 briefing note 19 http://www.who.int/csr/disease/swineflu/notes/briefing_20091203/en/index.html

Oseltamivir Resistance in Immunocompromised Hospital Patients

According to the latest WHO briefing, there have been two recent clusters of patients infected with oseltamivir-resistant H1N1 viruses reported to the agency. The first cluster occurred in Wales, UK in October 2009, and the second in North Carolina, USA in mid October to November.

Both clusters occurred in a single ward in a hospital in each area, and both involved patients whose immune systems were severely compromised or suppressed. Transmission of resistant virus from one patient to another is suspected in both outbreaks.

The emergence of drug-resistant influenza viruses in severely immunocompromised patients undergoing antiviral treatment is not unexpected, and has been well documented during seasonal influenza. Virus replication can persist in such patients for prolonged periods of time despite antiviral treatment, creating an environment in which drug-resistant viruses can readily be selected.

In the North Carloina cluster, three of the four cases were fatal, but the role of H1N1 infection in contributing to these deaths is uncertain. All of the resistant viruses in both clusters carried the same H275Y mutation, indicating resistance to oseltamivir, but not to the second antiviral drug, zanamivir.

Experts agree that severely immunocompromised patients need to be regarded as an especially vulnerable group, and as early signs of influenza may be masked by symptoms associated with underlying disorders or their treatment, the experts further agreed that doctors treating such patients should operate with a high level of suspicion for influenza virus infection and be especially vigilant for the rapid development of oseltamivir resistance.

In these patients, standard treatment doses and duration for treatment with oseltamivir are unlikely to be sufficient. Though clinical judgement is important, doses may need to be increased and continued, without interruption, for the duration of acute illness. Zanamivir should be considered as the treatment of choice for patients who develop prolonged influenza illness despite treatment with oseltamivir.

Once oseltamivir resistant virus has been detected in a ward treating severely immunocompromised patients, doctors should consider switching to zanamivir as the antiviral drug of first choice for treatment and when considering post exposure prophylactic treatment of other patients on the ward.

Source: WHO Pandemic (H1N1) 2009 briefing note 18 http://www.who.int/csr/disease/swineflu/notes/briefing_20091202/en/index.html

CDC - Preparing for the Flu: A Communication Toolkit for Schools

The CDC has come up with an Influenza communications toolkit for schools to provide basic information and communication resources to help school administrators implement recommendations from CDC’s Guidance on 2009 H1N1 and seasonal influenza during the 2009-2010 school year.

The toolkit includes:

• Fact sheets for schools and teachers on possible action steps to prevent spread of the flu.
• Fact sheets to inform parents on necessary action steps if a sick child is dismissed from school and must stay home.
• Fact sheets to inform parents of children who may be at high risk for complications from the flu.
• Template letters for schools to send to parents about steps the school is taking to prevent spread of the flu.
  

Posters for schools about influenza prevention as well as the entire toolkit are available on the CDC website at http://www.cdc.gov/h1n1flu/schools/toolkit/

U.S. finds pandemic H1N1 virus in turkey flock

By Charles Abbott

The pandemic H1N1 flu virus was confirmed in a flock of breeder turkeys in Virginia -- the first U.S. case involving turkeys, the U.S. Agriculture Department said on Monday.

The virus also has been found in hogs, three house cats, pet ferrets and a cheetah in California. USDA said infections of turkeys have been reported in Canada and Chile.

"This is the first detection of 2009 pandemic H1N1 influenza in turkeys in the United States," said a USDA spokesperson.

"There is a possibility that a worker, who was sent home ill with flu-like symptoms, could have infected the turkeys as a result of the artificial insemination processes, as the worker was a member of the insemination crew."

USDA said PEOPLE CANNOT GET 2009 H1N1 FROM EATING TURKEYS.

Swine flu viruses are known to affect quails and turkeys periodically, said USDA. USDA's Agricultural Research Service conducted two studies this year to see if the H1N1 pandemic virus could affect turkeys or other domestic fowl. Five turkey samples collected in mid to late November contained the virus.

http://www.reuters.com/article/internal_ReutersNewsRoom_ExclusivesAndWins_MOLT/idUSTRE5AT5P720091130

CDC Addresses Reports of Changes in the 2009 H1N1 Virus

As of November 24, 2009, there have been occasional reports of small changes in the genes of some virus samples collected from some people infected with 2009 H1N1 in several countries, most recently in Norway.

The public health implications of these changes are currently being studied by CDC and WHO scientists, but preliminary results at this time imply that, these changes appear to occur sporadically and spontaneously. No links between the small number of patients infected with 2009 H1N1 virus with these changes have been found, and viruses with these changes do not appear to be spreading to other people. According to the CDC, although further investigation is underway, there is no evidence that these changes in the 2009 H1N1 virus have lead to an unusual increase in the number of 2009 H1N1 infections or to a greater number of severe or fatal cases. Worldwide, these changes have been found in mild cases of 2009 H1N1 illness as well as severe cases of illness that have resulted in death. As a result, the public health significance of this finding remains unclear.

According to CDC and WHO experts, the 2009 H1N1 vaccine will still protect against these viruses, and there will not be any changes in the effectiveness of antiviral drugs to treat the illness.

Countries in addition to Norway that have reported these changes include Australia, Brazil, China, Japan, Mexico, Saudi Arabia, Ukraine, Uruguay and the United States.


http://www.cdc.gov/h1n1flu/in_the_news.htm#c

AED Connections - Field Studies Inform Efforts to Prevent Avian Flu

The Academy for Educational Development (AED) released an edition of AED Connections with a featured article on avian influenza:

Field Studies Inform Efforts to Prevent Avian Flu

By Tula Michaelides

Headlines such as “The Bird Flu: The Race to Prevent a Global Epidemic” and “The Next Killer Flu. Can we stop it?” abounded in late 2005. That’s when AED started reaching out to rural backyard poultry farmers in Southeast Asia—then the epicenter of bird flu outbreaks—with messages about how to protect themselves and their flocks from the destructive disease and‚ ultimately‚ improve their practices and behaviors.

As AED began its work on the Avian Influenza Behavior Change Communication project, funded by USAID, one thing became clear: little was known about this target audience in general‚ or about its perceptions of avian influenza in particular.

“AED quickly fielded a Knowledge‚ Attitudes‚ and Practices survey in Cambodia‚ Indonesia‚ Lao PDR‚ and Indonesia‚” said Robert Kelly‚ the project’s research director. “The initial research findings provided an understanding of what these farmers do that could put them at risk‚ and gave insight into their core values that would allow or prevent them from accepting change.”
The surveys were a form of risk­mapping‚ which helped to identify not only the dangers‚ but also what actions could mitigate those threats‚ Kelly added. The findings showed that the farmers were reluctant to pen their birds because doing so would be expensive, and they did not believe that caging the birds would prevent avian influenza.

Using this information‚ AED designed interventions the farmers would use, such as constructing small cages from local materials. Once one farmer adopted a certain practice‚ others in the community usually would follow suit.

‘Too Much Information’
In addition‚ the avian influenza messages that were created early in the epidemic included a lot of information‚ which tended to overwhelm people.
Long lists of H5N1 virus symptoms were disseminated in calendars‚ posters‚ lectures‚ and news coverage. But people still did not know the difference between H5N1 and the common poultry diseases they had been dealing with for years.

“This ‘too much information syndrome’ led to confusion among these farmers and no reporting of sick poultry since they couldn’t distinguish one disease from the other‚” said Anton Schneider‚ a senior communication specialist for the project. ‘So AED stressed the one critical message—that avian influenza causes sudden death in large numbers—and subsequently started to see an increase in reporting.”

AED’s research found that the media‚ friends‚ and family members were the primary sources of information for farmers. However‚ when researchers asked the families what they actually did in the event of an emergency‚ they discovered that the people looked to their local authorities for guidance.

As a result‚ AED provided village leaders and health workers with comprehensive training packages to inform them about avian influenza and better equip them to respond to their communities’ concerns.

Supply Chain Intervention
To use resources effectively in combating infectious diseases, it is important to conduct risk­mapping and identify hot spots‚ according to Kelly. AED analyzed the supply chain to determine potential opportunities for the virus to enter the system.
The research identified the key players—such as farmers‚ transporters‚ vendors‚ and consumers—what they knew‚ and what was important to them. The results showed much room for improvement.

“We discovered that biosecurity practices were lacking at all levels of poultry operations‚” said Schneider. “Hand hygiene and cleaning practices were abysmal‚ and community veterinary officials to help farmers improve practices were scarce.”
To address the problems and help control the spread of avian influenza in the supply chain‚ AED created awareness campaigns using effective teaching materials‚ knowledgeable trainers‚ and local media.

In the end‚ AED’s avian influenza projects conducted more than 50 qualitative and quantitative studies in more than 25 countries‚ and researchers have made their methodologies and instruments available to other organizations to assist in their studies.

For more information and to access the research studies visit http://www.avianflu.aed.org/.

Source: http://www.aed.org/aedconnections/Fall%202009/Features/ghpn.htm

H1N1 Vaccine Trial in HIV Positive Individuals

Researchers at the University of Florida Center for HIV/AIDS Research are currently conducting a national clinical trial on the 2009 H1N1 vaccine in HIV positive individuals. People with HIV are included in the list of high risk groups that are more vulnerable to complications from the flu due to their immunocompromised state.

The researchers aim to find out whether a higher-than-usual dose of vaccine will trigger a protective immune response in these individuals. Currently, adults have been shown to respond to only one dose of the vaccine, and this study is investigating whether HIV positive patients will have an immune response to one dose as well, or whether they will need two. The researchers will also be looking at how strong the immune response is in these individuals as well as how long the response lasts.

For more information on the trial, visit http://www.gainesville.com/article/20091123/ARTICLES/911231006/1002

Mutated influenza A(H1N1) 2009 detected in Norway

The Norwegian Institute of Public Health reported today that it detected an unusual mutation in three individuals; two of whom were the first fatal cases of influenza A (H1N1) 2009 in the country, and one of whom has severe illness.

The Norwegian Institute of Public Health reported on these detections, as did WHO (also see links to reports below). The Norwegian public health agency subsequently analyzed isolates from more than 70 patients infected with influenza A (H1N1) 2009 who manifested clinical illness, and no further instances of mutation were detected. These findings suggest that the mutation is not widespread in the country.

WHO reports that worldwide, laboratory monitoring of influenza viruses has detected a similar mutation in viruses from several other countries (with the earliest detection occurring in April), including Brazil, China, Japan, Mexico, Ukraine, and the US. No evidence currently suggests these mutations are leading to an unusual increase in the number of H1N1 2009 infections or a greater number of severe or fatal cases.

Dr. Anne Schuchat of the U.S. Centers for Disease Control and Prevention mentioned in a media briefing today that while this mutated virus is unusual, it sporadically has been detected in the US, though typically associated with more mild disease.

What are the implications of viral mutation?

• Viral mutations are normal; this specific mutation detected by the Norwegian Institute of Public Health probably will be of little or no importance (per Norwegian Institute of Public Health).
• This specific viral mutation is associated with the virus's virulence and ability to live deeper in respiratory tissue.
• Current data suggest this viral mutation has no implications for pandemic influenza A (H1N1) vaccine match or antiviral efficacy.
• The public health implications of this mutation are unclear, and may be difficult to assess (per WHO and Dr. Schuchat). It is important to note, however, that WHO reports there is no current evidence suggesting this mutation is leading to an unusual increase in the number of H1N1 2009 infections or a greater number of severe or fatal cases.
• To date, no links between the small number of patients infected with the mutated virus have been found, and the mutation doesn't appear to be spreading.

Sources:

Norwegian Institute of Public Health: http://www.fhi.no/eway/default.aspx?pid=233&trg=MainLeft_5669&MainLeft_5669=5544:81363::0:5667:1:::0:0

WHO: http://www.who.int/csr/disease/swineflu/notes/briefing_20091120/en/index.html

CDC media briefing: http://www.cdc.gov/media/transcripts/2009/t091112.htm

H1N1 and the 2009 Hajj

The Ministry of Health of Saudi Arabia has recently issued a set of health requirements and recommendations for entry visas for Saudi Arabia for the Hajj and Umra season, with special focus on reducing the transmission of pandemic (H1N1) 2009 influenza among pilgrims.

These health requirements and recommendations call for those population groups who are considered to be at high risk for complications from influenza to refrain voluntarily from this year’s Hajj. The requirements issued by the Kingdom also request the health authorities in pilgrims’ countries of origin to educate and advise pilgrims on basic public health measures (personal hygiene measures, cough etiquette, use of antiseptic hand gel, etc.) to be followed during Hajj and Umra to prevent the spread of pandemic (H1N1) 2009 during the upcoming Hajj season.

There are some concerns about transmission in the Middle Eastern region because despite the preferred WHO/CDC nomenclature of 'influenza pandemic (H1N1) 2009 virus', the misleading name 'swine flu' is used more often than not. Joining the Arabic word for swine (transliterated 'alkhanaazeer') leaves an impression in a subset of the population that, there being no local swine population, the risk of transmission to animals is nil.

By some estimates, the Hajj is the single largest, annual gathering in the world; the pilgrimage of Muslims to Mecca attracts between 2 and 3 million visitors from all over the globe. In Saudi Arabia, health officers have been stationed at all points of entry, and some airports have even been equipped with heat sensors to detect people with high fevers. Officials have also recommended that travelers get vaccinated, but not all countries are going to be able to inoculate all pilgrims before they leave for Mecca. With low vaccine supplies globally, it's a problem that is likely to be repeated at other world events.

WHO posts a briefing note on the safety of pandemic vaccines

From WHO:

"To date, WHO has received vaccination information from 16 of around 40 countries conducting national H1N1 pandemic vaccine campaigns. Based on information in these 16 countries, WHO estimates that around 80 million doses of pandemic vaccine have been distributed and around 65 million people have been vaccinated. National immunization campaigns began in Australia and the People’s Republic of China in late September.

Vaccination campaigns currently under way to protect populations from pandemic influenza are among the largest in the history of several countries, and numbers are growing daily. Given this scale of vaccine administration, at least some rare adverse reactions, not detectable during even large clinical trials, could occur, underscoring the need for rigorous monitoring of safety. Results to date are encouraging.

Common side effects
As anticipated, side effects commonly reported include swelling, redness, or pain at the injection site, which usually resolves spontaneously a short time after vaccination.
Fever, headache, fatigue, and muscle aches, occurring shortly after vaccine administration, have also been reported, though with less frequency. These symptoms also resolve spontaneously, usually within 48 hours. In addition, a variety of allergic reactions has been observed. The frequency of these reactions is well within the expected range.

Guillain-Barre syndrome
To date, fewer than ten suspected cases of Guillain-Barre syndrome have been reported in people who have received vaccine. These numbers are in line with normal background rates of this illness, as reported in a recent study. Nonetheless, all such cases are being investigated to determine whether these are randomly occurring events or if they might be associated with vaccination.

WHO has received no reports of fatal outcomes among suspected or confirmed cases of Guillain-Barre syndrome detected since vaccination campaigns began. All cases have recovered. WHO recommends continued active monitoring for Guillain-Barre syndrome.

Investigations of deaths
A small number of deaths have occurred in people who have been vaccinated. All such deaths, reported to WHO, have been promptly investigated. Although some investigations are ongoing, results of completed investigations reported to WHO have ruled out a direct link to pandemic vaccine as the cause of death.

In China, for example, where more than 11 million doses of pandemic vaccine have been administered, health authorities have informed WHO of 15 cases of severe side effects and two deaths that occurred following vaccination. Thorough investigation of these deaths, including a review of autopsy results, determined that underlying medical conditions were the cause of death, and not the vaccine.

Safety profile of different vaccines
Campaigns are using nonadjuvanted inactivated vaccines, adjuvanted inactivated vaccines, and live attenuated vaccines. No differences in the safety profile of severe adverse events among different vaccines have been detected to date.

Although intense monitoring of vaccine safety continues, all data compiled to date indicate that pandemic vaccines match the excellent safety profile of seasonal influenza vaccines, which have been used for more than 60 years. "

Source: http://www.who.int/csr/disease/swineflu/notes/briefing_20091119/en/index.html

WHO releases revised interim planning considerations for mass gatherings

WHO released an 8-page document outlining revised guidance for event planners.

In the document, entitled Interim planning considerations for mass gatherings in the context of pandemic (H1N1) 2009 influenza, authors recommend that event planners conduct a thorough risk assessment, in partnership with local and national public health authorities, prior to the event.

Highlighted considerations include:

• Level of influenza activity
• Period of time over which the gathering will take place - this has implications for when event-based cases would begin experiencing signs and symptoms of the flu (e.g., during the event if the event lasts longer than 2-3 days [the typical incubation period for flu] vs. afterward for events with shorter durations), and the type of resources (e.g., health care professionals, essential medical supplies/equipment, etc.) planners should have on hand during the event
• Age of participants
• Occurrence of severe disease and health care capacity

The guidance document can be downloaded free of charge at: http://www.who.int/csr/resources/publications/swineflu/h1n1_mass_gatherings/en/index.html

WHO 2009 H1N1 Weekly Update

13 November 2009 -- As of 8 November 2009, worldwide more than 206 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including over 6250 deaths.

For additional information related to geographic spread of influenza activity, qualitative indicators, and virological surveillance data, view the weekly report in its entirety at: http://www.who.int/csr/don/2009_11_13/en/index.html

WHO Rushes Drugs to Nations Hit by 2009 H1N1

Via Pam Belluck of The New York Times - excerpts:

“Emergency supplies of antiviral drugs are being sent to Ukraine, Afghanistan and other countries in Eastern Europe and Central Asia, where hospitals report that they are being overwhelmed by patients with swine flu, the World Health Organization said Thursday….

The new guidelines say that anyone with flu-like symptoms for three days, along with people in several high-risk groups — pregnant women, children under 2 and people with underlying respiratory problems — should not wait for laboratory tests to confirm the diagnosis but should be treated right away with drugs like Tamiflu.

‘The pandemic virus can cause severe pneumonia even in healthy young people,’ Dr. [Nikki] Shindo [a medical officer with the organization’s global influenza program] said, adding that “the virus can take life within a week….’ ‘The window of opportunity is very narrow to reverse the progression of the disease,’ she said. ‘The medicine needs to be administered before the virus destroys the lungs.’

Although antiviral medications are most effective when used within 48 hours after symptoms start, Dr. Shindo said the drugs should be given even after that if a person is very sick.

Dr. Shindo said the guidelines, similar to those in use in the United States, had not been adopted sooner because the agency was not yet confident, as it is now, about the safety and efficacy of the antivirals, Tamiflu and Relenza. Doctors there were also worried about shortages.

The agency said the countries most affected were Afghanistan, Mongolia, Belarus, Ukraine, Azerbaijan and Kyrgyzstan. The first four have already been sent supplies; the other two are to receive them soon.

‘Doctors involved in caring for very sick patients in intensive care units regretted that the patients arrived too late and even the most sophisticated medical procedures could not save their lives,’ she said. ‘We asked what could have been done differently to avoid the tragic outcomes. All of them answered, without exception, that things may have been very different if they had been treated with an antiviral drug earlier.’

Although Tamiflu had been stockpiled, protocol required doctors to prove a patient had H1N1 with laboratory testing before prescribing the medicine, said Nadezhda Rudnitskaya, the chief of pulmonology at Lviv Medical University.”

View the entire article at: http://www.nytimes.com/2009/11/13/world/13flu.html?_r=2

WHO - Clinical management of human infection with new influenza A (H1N1) virus: revised guidance

WHO released revised guidance for clinical management of persons infected with 2009 H1N1. The 15-page document provides information on an array of topics; including guidance for clinical management in resource-poor settings, and examples of clinical triage algorithms for ILI and pneumonia.

The document provides information/guidance on the following:

• Risk factors for severe disease


• Case descriptions (uncomplicated influenza, complicated influenza, signs and symptoms of progressive disease)


• Infection control


• Diagnosis


• General treatment considerations


• Antiviral therapy


• Care of severely ill patients (initial evaluation, antiviral therapy, supportive care, adjunctive pharmacologic therapy, secondary bacterial pneumonia)


• Resource poor settings


• Examples of clinical triage algorithms for ILI and pneumonia

The guide can be viewed in its entirety at: http://www.who.int/csr/resources/publications/swineflu/clinical_management/en/index.html