Adjuvants: Concerns temper the promise of the vaccine technology

In recent months, two major vaccine manufacturing power-houses (GSK and Sanofi-Pasteur) have announced results of clinical trials of pre-pandemic H5N1 vaccine using adjuvant, an antigen-sparing technology that may exponentially increase the manufacturing capacity of vaccine - particularly critical in a pandemic situation. In light of use of adjuvants, the WHO ramped up its forecast of available vaccine courses from a few hundred million to 4.5 billion (2 billion short of the projected global need, assuming mechanisms are in place to distribute the vaccine to everyone).

"(Adjuvants are chemicals that are incorporated in some vaccines to improve response to the vaccines' active ingredient. Adjuvants make it possible to reduce the dose of antigen in a vaccine without dampening the immune response.)"

Adjuvant presents obstacles though - some immunologic and others regulatory. The tradeoff of a possibly less safe vaccine may be acceptable in a pandemic - and regulatory hurdles (a particular problem in the US) are likely to be bypassed or sped up in a pandemic. Even so, concern remains.

"While adjuvants hold the greatest promise for dose-sparing, they also provoke trepidation because they are by definition immune-system activators. While many have been tested over the years, few have entered the market, because they proved too reactogenic to be acceptable to consumers or safe. Only one set of adjuvants, aluminum salts or alum (aluminum hydroxide, aluminum phosphate, and potassium aluminum sulfate), is licensed in the United States. Aluminum adjuvants and MF59, an oil-in-water emulsion that contains squalene (an oil found in some fish oils), are licensed in Europe."

"I have heard a lot of people say they expect problems with adjuvanted vaccines," said Hedwig Kresse, an associate analyst for infectious diseases with the British-based market analysts Datamonitor. "It is a technology that definitely has some potential, but there are a lot of issues that need to be addressed first".

Full story: http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/oct3007panvax4.html

Pandemic hysteria leads to overstocking of Tamiflu

During the height of hysteria about the possibility of a pandemic flu, New Zealanders began placing orders en masse for the best known defense against a possible pandemic: Tamiflu. Many other nations experienced similar reactions.

"Between 12 and 18 months ago, people had rushed to place orders for Tamiflu, saying they would wait up to six months for the drug to arrive. However, interest in bird flu seems to have waned "

Now, many pharmacy shelves are overstocked with the drug, as many of those rushing to place orders last year no longer want it.

"Pharmacy Guild of New Zealand president Steve Wise said ironically about a year ago you could not get Tamiflu "for love nor money", but there was now a surplus."

New Zealand doesn't expect to be able to exhaust its current stocks through treatment of seasonal flu. The current stocks expire in 2010, and the over-purchasing of the drug has raised concerns that much of the stocks will simply go to waste.

Full story: http://www.stuff.co.nz/4253690a11.html

Indonesian Boy Tests Positive for H5N1

A three-year-old Indonesian boy has tested positive for H5N1. The boy is from the same neighborhood in Tangerang, a city west of the capital of Jakarta, as the five-year-old girl who died of bird flu last week. Her death was the 89th fatality in Indonesia due to the virus. Fortunately, the boy has only experienced mild flu symptoms and is receiving treatment at Sulianti Saroso hospital in Jakarta.

"Indonesia, which has now had 111 confirmed cases of the disease in humans, has suffered more fatalities than any other country.
Excluding the latest case, there have been 204 deaths and 332 cases globally since 2003, according to World Health Organization data. "

Story from Reuters AlertNet: http://www.alertnet.org/thenews/newsdesk/JAK14415.htm

Burmese junta bans news on H5N1

Censorship boards of the Burmese junta have banned news broadcasts within the nation regarding a new outbreak of H5N1 in Burma, an outbreak confirmed by journalists on October 20.

"The latest H5N1 bird flu outbreak was reported to the OIE-World Organization for Animals on October 24 by the regime's Livestock Breeding and Veterinary Department, according to the OIE Web site. The Burmese report sent to the OIE said the bird flu outbreak killed 400 chickens and ducks. The authorities reportedly killed 33,459 fowl to try to contain the virus."

This is the first reported outbreak among foul since July.

Full story: http://www.irrawaddy.org/article.php?art_id=9138

Another Outbreak in Vietnam

More than 290 ducks were found dead at a small farm in the central province of Quang Tri, Vietnam that tested positive for H5N1. The dead ducks were part of a flock of 600 5-day-old ducklings that had not been vaccinated. The rest of the flock was culled to prevent further spread of the disease, the farm was disinfected, a ban has been placed on poultry transport from the farm, and poultry at neighboring farms have been vaccinated. Earlier in October there was an outbreak reported in the Mekong Delta province of Tra Vinh which was the first in Vietnam in more than two months.

"Vietnam's aggressive poultry vaccination program has been seen as key to controlling the disease in birds and deny it opportunity to jump to humans.
So far this year, Vietnam has vaccinated 62.6 million birds, including 39.4 million ducks and 23.2 million ducks."

http://www.bangkokpost.com/breaking_news/breakingnews.php?id=122965

H5N1 may become endemic in parts of Europe

After German scientists discovered the H5N1 virus in dead domestic ducks, experts are recommending that Europe prepare for future outbreaks of avian influenza. If it persists in wild waterfowl throughout the year, Europe could become the third continent where the H5N1 strain is endemic. "It could well be that there is more virus circulation in Europe than currently assumed," said Food and Agriculture Organization (FAO) senior animal health officer Jan Slingenbergh.

"FAO veterinary experts said they were particularly concerned about the Black Sea area where a high concentration of chickens, ducks and geese is comparable with virus-entrenched Asia.
Experts urged the European countries to boost their H5N1 monitoring and surveillance schemes in all regions with big duck and geese production."

"We are not saying that the virus is widely spread in European countries, in fact most of the countries are currently virus-free. But undetected localised virus spots in countries with significant waterfowl may pose a continuous risk."

Full story at: http://uk.reuters.com/article/topNews/idUKL2510016520071025

89th Death in Indonesia

The Ministry of Health has reported the 89th death in Indonesia, a four year old girl from Tangerang.

http://www.depkes.go.id/en/2410an.htm

Reuters reports that poultry had died in the girl's neighborhood a week before -

"The four-year-old girl died on Monday after being admitted to hospital two days earlier, health ministry spokeswoman Lili Sulistyowati said by telephone. The girl, who had been suffering from fever, died after being transferred to Persahabatan hospital in Jakarta.

Officials were still investigating the case, but four chickens had previously died in the girl's neighbourhood, another official at the ministry's bird flu centre said.

Contact with sick fowl is the most common way for humans to contract the deadly H5N1 strain of the virus.

Bird flu is endemic in bird populations in most parts of Indonesia, where millions of backyard chickens live in close proximity with humans.

Indonesia, which has now had 110 confirmed cases of the disease in humans, has suffered more fatalities than any other country."

http://www.alertnet.org/thenews/newsdesk/L23739948.htm

Good News on Pandemic Flu Vaccine?

Massive investments in vaccine manufacturing capacity and innovative vaccine technologies have paid off, says the WHO. Now the world's capacity to manufacture vaccine in the event of a pandemic is far greater than predicted last year.

"Last spring, the World Health Organization (WHO) and vaccine manufacturers said that about 100 million courses of pandemic influenza vaccine based on the H5N1 avian influenza strain could be produced immediately with standard technology. Experts now anticipate that global production capacity will rise to 4.5 billion pandemic immunization courses per year in 2010."

Even with this heartening advance, this is still 2 billion courses short of what would be needed in the first 6 months for the world.

From WHO: http://www.who.int/mediacentre/news/releases/2007/pr60/en/index.html

The new Communications Initiative Website

The Communications Initiative has recently updated and revamped their websites so they are more user friendly. Their avian influenza website is fantastic! I would definitely bookmark and visit often. It has great tools and information about AI & Pan flu work around the world. You can also sign up to receive their AI updates.

http://www.comminit.com/en/avianinfluenza.html

In the event of a pandemic, who will be first priority for a vaccine?

The International Herald Tribune posted this story on the US plan for vaccinations during a pandemic.

"Pregnant women, babies and toddlers would join doctors, emergency workers and soldiers at the head of the line for scarce vaccine if a super-strain of flu triggers the next pandemic, says a draft U.S. government plan to be released Tuesday.

Once more vaccine is brewed, older children along with workers who keep the electricity, water and phones running could be next to roll up their sleeves.At the end of the line: The elderly and healthy younger adults.

It is a priority list quite different from the usual winter pleas for older Americans to get vaccinated against regular flu. And it reflects growing agreement that curbing a super-flu would require protecting workers who care for the sick and maintain crucial services — plus targeting the people most likely to spread flu, not just die from it.

"Children are not only highly susceptible to influenza, children are also very good at spreading it," said William Raub, emergency planning chief at the Department of Health and Human Services. "Protecting them also protects those in the population."

http://www.iht.com/articles/ap/2007/10/22/america/NA-GEN-US-Pandemic-Vaccine.php

Vietnamese government to communities: Vaccinate and remain alert

Vietnam's director of the ministry’s Animal Health Department, Bui Quang Anh, said today that another H5N1 outbreak among poultry is likely and that, together, diligence, vaccination , and keeping smuggled poultry from entering the country are key to preventing future outbreaks.

After the government provided 90 million doses of vaccine for poultry to communities, half of 64 targeted cities have completed vaccination - ahead of schedule. However, in localities slow to vaccinate and prepare for H5N1, there have been more outbreaks.

"We have learned that in the areas where local authorities have carefully guided people to prevent outbreaks and given timely financial support, the outbreaks have been better controlled," Anh said.

The ministry has asked that for reprimands of "chairmen of provincial people’s committees who have not carried out vaccination programmes, causing the return of bird flu."

In addition, authorities plan to relocate poultry and egg hatcheries to areas "outside city limits, away from residential areas, universities, schools, hospitals, markets, offices and public areas" to reduce the risk of further spread and transmission to humans. It is not clear how the government plans to implement this policy.

Full story: http://vietnamnews.vnagency.com.vn/showarticle.php?num=03AGR191007

Indonesia's reported 89th H5N1 death NOT H5N1, says Minister of Health

A young girl, testing positive for H5N1 after an initial test, was said to be Indonesia's 89th human death from H5N1. However, after a second test was performed, the Ministry of Health is now reporting that she did not die of H5N1, though they have not reported an alternate cause of death.

"The 10-year-old was admitted to hospital on Saturday suffering symptoms that led doctors to suspect she could be carrying the H5N1 virus ..."

If the ministry result is positive, a second test is carried out at a separate laboratory before a patient is confirmed as infected with bird flu in Indonesia.

The young girl's aunt, who presented with similar symptoms, also died over the weekend.

Full story, via H5N1 blog: http://news.yahoo.com/s/afp/20071022/hl_afp/healthfluindonesia_071022161333;_ylt=A9G_Rz3P0hxHFEcBjiWTvyIi

Demand for animal products will increase the need for food safety

As the population of the world continues to expand by about 78 million people per year, the demand for animal products will also increase. With this increase comes the necessity for ensuring the safety of our food resources.
"The growing population will increase the demand for animal products coming from developing countries" said Francois Le Gall, of the World Bank. Le Gall also agrees with Bernard Vallat, the director of the World Organization for Animal Health, that only 40 out of 200 countries could respond to a health crisis that originates from animal disease."
For instance, to date, avian influenza has forced the culling of about 100 million birds in Asia, especially in Vietnam. Other problems include farmers embracing antibiotics a little too fully, and causing antibiotic resistance in their livestock.
Anni McLeod of the UN Food and Agriculture Organization (FAO) says "more genetic diversity may be needed in the future. In poultry, for example, there are about three or four companies that control most of the poultry breeds in the world. If nothing is done to prevent diseases in livestock for human consumption the world could face a major crisis in the next 10 years."
In order to meet this coming challenge, international organizations are working together on several fronts of the issue such as "food safety, veterinarian services, packing, and transportation."

Click here to view the full story: http://www.flulab.com/overview.php?a=2007-10-16-fl54

Summit on Business Preparedness for Pandemic Influenza

This speech, given by WHO Director-General Margaret Chan, was delivered February 5, 2007 at CIDRAP's Summit on Business Preparedness for Pandemic Influenza in Orlando, FL. It remains an up-to-date statement which addresses two main issues: "the assessment of threat as perceived by staff and experts at WHO, and a description of what might occur during the first influenza pandemic of the 21st century."
In assessing the pandemic, the Director-General said "H5N1 has been circulating in poultry in Asia since at least mid-2003. It has caused the largest outbreaks in birds and the highest number of human cases on record for any avian influenza virus. Over the years the virus has lost none of its persistence in nature and non of its virulence for humans. Experts concluded that the threat is not likely to diminish in the near future and that the virus has evolved in alarming ways in domestic poultry, migratory birds, and humans in the past four years. Also, H5N1 survives longer in the environment and at higher temperatures, and are more lethal to chickens. Yet another alarming development is that we've lost one of our warning signs to the virus. Domestic ducks can now become infected and excrete large quantities of lethal virus, yet show no signs of illness. "
In her description of what we might expect to see during a pandemic, Dr. Chan said the following: "all countries will be affected, international spread will be rapid, widespread illness will occur, excess mortality will occur, medical supplies will be inadequate, hospital capacity will be inadequate, and economic and social disruption will occur."

For the full presentation, please visit: https://umconnect.umn.edu/chan/

Updated guidelines from WHO

WHO has recently updated their guidelines for containing an outbreak in the initial stages of a pandemic

"Changes to this version of the protocolThis document replaces previous versions of the protocol. In brief, key changes include:

• More emphasis on rapid containment and less on rapid response which is covered in WHO guidelines for invetigation of human cases of avian influenza A(H5N1) published in 2007.
• An expanded discussion of the decision-making process.
• Refinement of the containment strategy emphasizing the localized geographical approach and describing the key activities for Containment and Buffer Zones.
• A proposed approach for estimating the duration of a containment operation.
• New or updated annexes on ethical issues, non-pharmaceutical interventions, communications and laboratory preparedness.
• Annexes on antiviral stockpile planning and preparedness issues are under revision and and will be added in the near future.

The protocol will be updated and revised as new information becomes available and more detailed guidance and tools are developed."

Updated WHO Interim Protocol: Rapid operations to contain the
initial emergence of pandemic influenza at
http://www.who.int/csr/disease/avian_influenza/guidelines/draftprotocol/en/

12 year old boy dies of H5N1 in Tangerang

The 12 year old boy with H5N1 in Tangerang, a city near Jakarta, passed away this weekend.

"The child, identified as Irfan, was brought to a local midwife on Oct. 3 after suffering from fever for three days, Head of Communicable Disease Control and Prevention Section at the Tangerang District Health Office dr Yuliah Iskandar said on Monday.As his health condition deteriorated, Irfan was later transferred to Tangerang Regional Hospital where he underwent a medical test on Oct. 8, Yuliah said.He was later moved to Persahabatan Hospital in Jakarta on Oct. 9 for further medical treatment as he had tested positive for bird flu based on the result of a laboratory test conducted by the Health Research and Development Agency and the Eijkmann Institute, she said.To anticipate the possible spread of the H5N1 virus in the area, the district health office had sent officers to Ceger village to take samples of the blood of Irfan`s relatives and neighbors, she said.Yuliah said Irfan did not have contact with dead chicken before being infected with the bird flu virus. Neither did his parents raise poultry in their backyard."But there is backyard poultry about 500 meters from the victim`s house," she said."

From Antara News: http://www.antara.co.id/en/arc/2007/10/15/ai-takes-another-life-in-tangerang/

More on how viruses interact with bacteria

Many deaths from influenza are actually caused by secondary bacterial infections. However, the link between influenza viruses and bacteria are not well understood. Researchers at St. Jude's are studying this question, which has public health preparedness implications for stockpiling antibiotics to prevent excess mortality.

"Dr. Jonathan A. McCullers from the Department of Infectious Diseases at St. Jude Children's Research Hospital in Memphis, Tennessee and colleagues examined this interaction by studying a newly discovered influenza A virus (IAV) protein, called PB1-F2. The gene encoding PB1-F2 is present in nearly all IAVs, including highly pathogenic avian IAVs that have infected humans and the IAV associated with the 1918 pandemic. "PB1-F2 was recently shown to enhance viral pathogenicity in a mouse infection model, raising questions about its effects on the secondary bacterial infections associated with high levels of influenza morbidity and mortality," explains Dr. McCullers.

The finding that PB1-F2 promotes lung pathology in primary viral infection and secondary bacterial infection also provides critical information for the future. "Given the importance of IAV as a leading cause of virus-induced morbidity and mortality year in and year out, and its potential to kill tens of millions in the inevitable pandemic that may have its genesis in the viruses currently circulating in southeast Asia, it is imperative to understand the role of PB1-F2 in IAV pathogenicity in humans and animals," says Dr. McCullers. "These findings also reinforce the recent suggestion of the American Society for Microbiology that nations should stockpile antibiotics for the next pandemic, since many of the deaths during this event are likely to be caused by bacterial super-infections."

New human H5N1 case in Indonesia

From Reuters: http://www.alertnet.org/thenews/newsdesk/JAK196146.htm

"A 12-year-old Indonesian boy has tested positive for bird flu, and is being treated in a Jakarta hospital, a health ministry official said on Thursday. The ministry's bird flu centre's Muhammad Nadirin said it was not clear how the boy from Tanggerang city in West Java, contracted the virus, but some chickens had died in his neighbourhood.
The most common way to contract the deadly virus is through sick fowl.

The disease is endemic in the bird population in most parts of Indonesia, where millions of backyard fowl are kept in close proximity to humans and where education campaigns often do not reach remote areas.

Muchtar Ichsan, a doctor at the hospital, said the boy has been taken to an isolated room and was on a respiratory device.

Indonesia has 109 confirmed cases of human bird flu, 87 of them fatal, the highest in the world.
Scientists are concerned the H5N1 virus could mutate into a form that passes easily between humans, triggering a pandemic in which millions could die."

Ghana: No compensation without bio-securiity measures

The Ghanan government announced today at the outset of a three-day workshop on prevention of H5N1 that it would no longer compensate farmers for lost or culled birds due to H5N1 if those farmers did not observe

During the last outbreak, the government compensated farmers for more than 27,000 lost birds without taking preventive measures into account. Since then, the Veterinary Services Directorate has begun training farmers on appropriaite measures to keep their poultry secure.

The workshop and simulation are co-sponsored by the Ghanan government with the Food and Agriculture Oragnisation (FAO) and USAID.

Full story: http://www.accra-mail.com/mailnews.asp?id=2848

Developments in Indonesia

Eight people suspected of being infected with H5N1 in Medan were all declared free of the virus. No new cases have been reported since the death last week of Linda Tismeri.

Tismeri, the 87th confirmed H5N1 death in Indonesia, traveled from her home in rural Riau to Jakarta to visit family after contracting the virus, raising concerns that she may have passed it on to others. The Indonesian government is following up her contacts to ensure there was no spread of the virus.

There is no evidence at this time of any spread.

Full story, via H5N1 blog: http://www.scottmcpherson.net/display/ShowJournal?moduleId=1366394&categoryId=116462

87th H5N1 death in Indonesia

"A 44-year-old woman from Indonesia's Sumatra island has died of bird flu, raising the toll in the nation worst affected by the disease to 87, the health ministry said Monday. Two samples taken from the woman tested positive for the H5N1 virus, the health ministry's bird flu information centre said in a press release."

"The ministry statement said it had not confirmed if the woman had been in contact with infected poultry, the usual method of transmission."

From Channel News Asia: http://www.channelnewsasia.com/stories/afp_asiapacific/view/304443/1/.html

Vietnam: All levels of government must participate in H5N1 prevention

At a seminar in Hanoi on October 5 attended by the Vietnam Ministry of Health and the US Centers for Disease Control and Prevention, the Director of the Preventive Health Department announced that though H5N1 is "temporarily under control", all levels of government - from the commune to the provincial level - must join together to ensure long-term prevention of H5N1 transmission.

The seminar was held to unveil modifications and additions to the government's plan to prevent human transmission of H5N1.

In addition to allowing local communities to take part in the implementation of avian influenza control, the Ministry announced it will establish 15 influenza management offices to monitor surveillance, take samples, and offer guidance and quarantine control to local officials.

Full text available online, via H5N1 blog: http://english.vietnamnet.vn/social/2007/10/748067/

An additional story on the seminar: http://www.nhandan.com.vn/english/life/061007/life_s.htm

Indonesia: Holidaymakers to help spread the word on H5N1 prevention

During the Idul Fitri holidays, more than 25 million Indonesians are expected to travel to their hometowns, many from Jakarta. The USAID-funded Community-Based Avian Influenza Control (CBAIC) program capitalized on the opportunity by approaching travelers at bus stations and terminals in Jakarta to encourage them to talk to their family members in their hometowns about avian influenza and ways to prevent its spread.

In addition, CBAIC provided the Primajasa bus company, which travels to many of the provinces affected by H5N1, with 21,000 seat covers containing a quiz and more detailed information about prevention of H5N1. CBAIC hopes this strategy will encourage discussion about H5N1 and spread prevention methods from urban centers to more rural areas.

http://www.thejakartapost.com/detailgeneral.asp?fileid=20071006173939&irec=13

Virus circulating in Africa and Europe could be more threatening to humans

Scientists at the University of Wisconsin-Madison are reporting important mutations in the H5N1 virus circulating in Africa and Europe

"Birds usually have a body temperature of 41 degrees Celsius (106 degrees F), and humans are 37 degrees C (98.6 degrees F) usually. The human nose and throat, where flu viruses usually enter, is usually around 33 degrees C (91.4 degrees F).
'So usually the bird flu doesn't grow well in the nose or throat of humans,' {Dr. Yoshihiro Kawaoka of the University of Wisconsin-Madison} said. This particular mutation allows H5N1 to live well in the cooler temperatures of the human upper respiratory tract."

Recent samples of the virus taken in Africa and Europe all had this particular mutation

http://www.alertnet.org/thenews/newsdesk/N04393544.htm

86th H5N1 death in Indonesia

From Komnas (http://www.komnasfbpi.go.id/berita_eng.php?id=16)


"Test results from the Health Research and Development Center of the Ministry of Health confirmed that a 21-year old man, known as "AR" from Cengkareng area in West Jakarta, is the most recent confirmed H5N1 case in Indonesia. Overall, Indonesia has now recorded 107 confirmed human H5N1 cases with 86 fatalities. The case fatality rate now stands at 80.37%. Up to today, DKI Jakarta has recorded 26 bird flu positive cases with 23 fatalities.
AR, experienced onset of illness on 18 September 2007. He was examined at Sumber Waras Hospital on 25 September 2007, where 2 days later he was moved to the ICU. AR died 28 September 2007 at Sumber Waras Hospital."