Vol. XII, No. 17 ~ EINet News Briefs ~ Aug 21, 2009

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Cumulative number of human cases of avian influenza A/(H5N1)
Economy / Cases (Deaths)
2009
China/ 7 (4)
Egypt/ 32 (4)
Viet Nam/ 4 (4)
Total/ 43 (12)

***For data on human cases of avian influenza prior to 2009, go to:
http://depts.washington.edu/einet/humanh5n1.html

Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 438 (262).
(WHO 8/11/09 http://www.who.int/csr/disease/avian_influenza/en/index.html )

Avian influenza age distribution data from WHO/WPRO:
http://www.wpro.who.int/sites/csr/data/data_Graphs.htm (WHO/WPRO 7/1/09)

WHO's maps showing world's areas affected by H5N1 avian influenza (last updated 5/10/09): http://gamapserver.who.int/mapLibrary/

WHO’s timeline of important H5N1-related events (last updated 7/29/09):
http://www.who.int/csr/disease/avian_influenza/ai_timeline/en/index.html

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Global: 'Original antigenic sin': A threat to H1N1 vaccine effectiveness?
Half a century ago, scientists reported evidence of some curious behavior by the immune system in humans and animals: If a host was exposed to an influenza virus and later encountered a variant strain of the same virus, the immune system responded to the second attack largely with the same weapons it used against the first one. Like an army still fighting by the tactics of the last war, the host immune system mostly produced antibodies matched to the first virus instead of the second, resulting in a less effective defense. With a nod to theology, this phenomenon was labeled "original antigenic sin."

Today, in the face of the pandemic H1N1 flu virus, many countries are preparing to launch H1N1 vaccination campaigns this fall. Millions of people are in groups recommended to receive both seasonal flu immunizations and H1N1 vaccinations. Seasonal flu vaccine—which contains an H1N1 component, distantly related to the novel H1N1 virus—will be available sooner in most places.

This timing has caused some observers to wonder: If a person gets a seasonal flu shot and then an H1N1 dose a few weeks later, will original antigenic sin come into play and cause a poor response to the H1N1 vaccine? Nobody knows the answer for sure, but leading flu and immunization experts say they aren't especially worried at this point. At the same time, they suggest the possibility bears watching. "For the time being there is no cause for worry especially for vaccines because the influenza vaccines are really . . . very well known in terms of the seasonal use of these," said Dr. Marie-Paule Kieny, director of the World Health Organization's Initiative for Vaccine Research.

But there is enough concern so that the H1N1 vaccine clinical trials recently announced by the US National Institute of Allergy and Infectious Diseases (NIAID) will look into the question. Two of the trials will examine whether giving an H1N1 vaccine and seasonal flu vaccine sequentially or simultaneously affects the immune response to either vaccine, according to the NIAID.
(CIDRAP 8/18/09)

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Global: Researchers suggest osteoporosis drugs may have antiviral benefits
Researchers from Hong Kong have found that two osteoporosis drugs, pamidronate and zoledronate, might have potential as treatment for influenza, including the novel H1N1 and the H5N1 viruses. They found that the two drugs triggered yd-T cells that killed flu-infected human cells. The next steps are to test the drugs in animals and conduct clinical trials in humans. The findings were released by the University of Hong Kong.

Full Reuters story available at http://www.reuters.com/article/asiaCrisis/idUSHKG233114.
(CIDRAP 8/14/09)

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"It was felt . . . it would simply be unacceptable to the UK population to tell them we had a huge stockpile of drugs but they were not going to be made available," Professor Robert Dingwall, a member of the Committee on Ethical Aspects of Pandemic Influenza, said. On 16 Aug 2009, one of the country's foremost flu experts called for the national helpline to be shut down to stop hundreds of thousands of doses of Tamiflu going out in an unregulated way, which could render it useless when a more dominant strain returns in the autumn.

As it became clear that the current outbreak only had mild symptoms, the committee recommended that antivirals should only be given to those in high risk categories, like pregnant women or people with existing respiratory illnesses. It suggested the government explain to people that they would not be given medicine they did not need and should use off-the-shelf flu treatments. Some members wanted to take a long-term view of the risk of resistance developing and to seek to preserve the effectiveness of antivirals for the next pandemic, which may be more severe. In July 2009, the government launched the national pandemic flu service, which authorized more than 511,000 courses of Tamiflu and Relenza treatment during its first fortnight in operation.

Oxford University researchers have warned that antivirals are not a "magic bullet" against flu and that resistance to the drug could develop, making it useless to fight any future and potentially more serious pandemic flu strain. The concern was seconded by flu expert Hugh Pennington, emeritus professor at Aberdeen University, who called for the national flu line to be shut down. "I am concerned about the vast amount of Tamiflu that is going out almost unregulated," he said. "We are increasing the possibility that the flu will become resistant sooner or later. At the moment, there is no desperate need for Tamiflu. We should be reconsidering its issue rather than encouraging its use. I think we should stop the national pandemic flu service. It was put there for an outbreak of far higher mortality than we have. If you get a resistant strain that becomes dominant in the autumn, Tamiflu will then be useless."

A senior government adviser, Prof Peter Openshaw, said the government was told during the early stages of the current outbreak of the "significant side effects" that Tamiflu was causing in some people. "I think there was, in some quarters, a slight over-optimism about the acceptability of prophylactic medication and its effectiveness," said Openshaw, a member of the Scientific Advisory Group for Emergencies. "Maybe some of the less clinical scientific advisers perhaps slightly over-inflated expectations of the ease and efficiency of antiviral treatment. Many of us who do clinical work and are clinically trained had a bit more of a jaundiced view of how things may turn out." Openshaw said antivirals were effective only if used within 36 to 48 hours of symptoms developing. "If the treatment is delayed, they are relatively ineffective. On the other hand, we do have this large stockpile available, and I think there is an advantage in trying to treat cases early in order to reduce the severity and the number of patients who end up needing hospital care." Such a policy could "blunt" a spike of cases, reducing pressure on health resources, he said.
(ProMED 8/17/09)

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UK: Agency says Tamiflu plus warfarin may increase stroke risk
Britain's Medicine and Healthcare Products Regulatory Agency (MHRA) is concerned that oseltamivir (Tamiflu) may interact with the anticoagulant warfarin to increase the risk of uncontrolled bleeding and stroke, according to a report by the Daily Mail newspaper. The agency has advised health professionals to be alert for such cases. The story said the MHRA has received reports of 12 suspected adverse reactions to oseltamivir that involved interactions with warfarin.
(CIDRAP 8/19/09)

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Victoria Agriculture Minister Joe Helper said tests confirmed the presence of influenza at the piggery after its owners reported earlier this week that the animals were not eating. “It is important to stress that this is not a human health issue and that national and international food authorities continue to advise that pork and pork products are safe to eat,” he said.

Media reports said the pigs were believed to have contracted the virus from workers at the property who were suffering the human form of the disease.
(ProMED 8/20/09)

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Australia: Young man survives near-fatal case of pandemic H1N1 with help of IV zanamivir
A 20-year-old Australian who has asthma survived a nearly fatal case of H1N1 flu after he was treated with an experimental intravenous form of zanamivir (Relenza). The man's lungs had filled with mucus and his stomach had shut down, ruling out treatment with oral oseltamivir. So his doctors decided to try IV zanamivir, which had to be flown in from the US. The drug is normally taken with an inhaler.
(CIDRAP 8/19/09)

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China: Firm claims good results in pandemic influenza H1N1 vaccine clinical trial
The Chinese company Sinovac Biotech said a single dose of its novel H1N1 vaccine generated an immune response and appeared safe in its first clinical trial on 18 Aug 2009. The firm asserted that the product met "international criteria for vaccines" and caused no severe side effects in 1,614 volunteers. The company said the results were the first reported for any H1N1 vaccine clinical trial. No details were released on the immune responses to different doses.
(CIDRAP 8/18/09)

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USA: 41 more pandemic H1N1 influenza related deaths
The number of novel H1N1 deaths in the United States rose to 477, up from 436 the previous week, the US Centers for Disease Control and Prevention said 14 Aug 2009 in its weekly update. Hospitalizations rose to 7,511, up from 6,506. Dan Jernigan, MD, MPH, with the CDC's Influenza Division, said that flu continues to decline, with widespread activity reported in four states. Officials are looking into reports of increased flu activity in Florida and North Carolina.
(CIDRAP 8/14/09)

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USA: Federal officials offer new pandemic H1N1 guidance for businesses
Federal officials released new guidance on 19 Aug 2009 to help businesses prepare for an expected resurgence of novel H1N1 activity during the upcoming influenza season, a document that clarifies how long sick workers should stay home and suggests ways to keep employees safe and business disruptions at a minimum.

Commerce Secretary Gary Locke said the business community can help limit the impact of the flu pandemic on society, but they need to strike the right tone with employees. "In America, we love to praise the puritan work ethic, but we praise common sense and responsibility for the health of coworkers and the productivity of companies," he said. Locke added that the new guidance suggests companies adopt flexible, nonpunitive sick-leave policies that support one of the most important measures for preventing the spread of the virus: staying home when sick. The recommendations advise against requiring a doctor's note for returning to work, because such requests are likely to further stress an overburdened healthcare system. Locke also emphasized the document's advice for businesses to plan now for spikes in absences as well as possible school closures.

Kathleen Sebelius, Department of Health and Human Services (HHS) secretary, said until a novel flu vaccine is available, employers can help mitigate the impact of the flu this fall by encouraging target groups to receive their seasonal flu vaccines. She said she hopes businesses will do some outreach ahead of time to encourage employees, especially those in high-risk groups such as pregnant women or young workers, to receive the novel H1N1 vaccine when it is available. She encouraged businesses to keep in touch with their local health departments, because flu conditions can change rapidly.

One of the key components of the guidance is a recommendation on when employees who have had flu-like symptoms can return to work: 24 hours after fever ceases without assistance from fever-reducing medication. That new recommendation reflects revised guidance from the US Centers for Disease Control and Prevention (CDC), released on 6 Aug 2009, on how long those who are sick with novel flu should stay home. Earlier recommendations urged people to stay home for 7 days after illness onset or for 24 hours after symptoms resolve, whichever was longer.

Janet Napolitano, secretary of the Department of Homeland Security (DHS), said federal officials expect novel H1N1 activity to pick up again as school resumes and that now is the time for businesses to review and tweak their pandemic plans. "You're dealing with a tough economy and may not have had time to think through what a bad flu season really is," she said.

The updated guidance is available at http://www.flu.gov/plan/workplaceplanning/guidance.html.
(CIDRAP 8/19/09)

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USA (Massachusetts): Communities of color disproportionately affected by pandemic H1N1 influenza
A disproportionate number of patients hospitalized with novel H1N1 flu in the Boston area have been African American or Hispanic, the city's public health officials have found. They speculate that urban crowding, high levels of chronic health conditions, and other issues related to poverty are contributing factors. Of 71 flu patients hospitalized, 49% were African American and 28% were Hispanic, rates double the groups' shares of the city population.
(CIDRAP 8/18/09)

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USA (New York): Mandates health workers obtain influenza vaccinations
The New York State Health Department is requiring tens of thousands of health care workers across the state to be vaccinated for flu, amid fears that pandemic influenza H1N1 will return in fall 2009. The new regulation, quietly adopted as an emergency on 13 Aug 2009, affects workers at hospitals, in home health care agencies and in hospice care, but, because of a technicality in state law, not in nursing homes.

The regulation raised protest 18 Aug 2009 from New York’s largest health care union, 1199 S.E.I.U. United Healthcare Workers East, whose president, George Gresham, said that the policy was “completely unprecedented” and could become punitive if the religious or cultural beliefs of workers prevented them from being vaccinated. “Health care workers on the front lines of providing care deserve the dignity and respect of thoughtful consideration before a regulation like this can just be rushed through and put into effect,” Mr. Gresham said.

Until now, flu vaccination has been voluntary, and fewer than half of health care workers have been vaccinated in a typical season, state health officials said. The new regulation, which requires vaccination against seasonal flu and the H1N1 virus, would affect workers and volunteers who come into direct contact with patients, including nurses, doctors and aides, and even nonmedical staff members like food service workers if they enter a patient’s room, a Health Department spokeswoman, Diane Mathis, said.

Ms. Mathis declined to comment on Mr. Gresham’s criticism, but said that health officials had met with the union and other professional associations to discuss the proposal before it was adopted. She said that vaccination was “clearly a patient safety issue.”
(NY Times 8/18/09)

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In May and June 2009, seven people contracted listeriosis after eating chicken wraps served on Virgin Blue flights out of Brisbane. Two of those passengers were pregnant women who gave birth prematurely.
(ProMED 8/20/09)

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China (Heilongjiang): Hemorrhagic fever outbreak ails 7
A city in northeast China's Heilongjiang Province has reported seven hemorrhagic fever cases, a local health official said on 17 Aug 2009. Zhang Yanjie, director of the Yichun municipal health bureau, confirmed the outbreak in a bid to dispel rumors on the Internet that stated the city had pneumonic plague cases. The seven people living in different parts of the forests in Jinshantun District contracted the disease between 28 Jul and 3 Aug 2009, he said. The patients are in stable condition. Investigations show that the patients drank water or ate food contaminated by mice.
(ProMED 8/17/09)

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Russia (Novosibirsk): Over 500 people hospitalized due to tick bites
According to the report by Novosibirsk oblast Rospotrebnadzor (public health agency), 241 people sought medical treatment following tick bites the first week of Aug 2009. Twenty-three of them have been hospitalized due to suspected tick-borne encephalitis virus infection. In 2009, there have been 16,302 visits to health care facilities following tick bites, 551 people have been hospitalized, and 128 cases have been confirmed including 22 children. There has been one fatal case. This is an increase over the same period in 2008.
(ProMED 8/7/09)

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Russia (Udmurtia): Hemorrhagic fever with renal syndrome situation continues to be unstable
According to the staff of Rospotrebnadzor (Federal Service for Consumer Affairs and Human Welfare) administration in Udmurtia the hemorrhagic fever with renal syndrome (HFRS) situation remains uncertain. The territory of Udmurtia is regarded as an optimal environment for voles, which are the main reservoir of HFRS infection. The epizootic situation in the forests of the Republic is unstable. The vole population has expanded; the numbers fluctuate between 21 and 60 percent of the maximum recorded. During the first seven months of 2009 a total of 306 cases of HFRS were registered, 17 percent lower than during the same period of 2008. In May 2009, the death of a 40-year-old man from HFRS was reported in the city of Ijevsk.

HFRS has been recorded in 17 districts and four cities of Udmurtia (Ijevsk, Mojga, Sarapul, Votkinsk). The forecast for this infection is not favorable. An increased morbidity is expected during the summer-autumn period due to expansion of the rodent population. Because the peak morbidity is expected during July and August 2009, it is recommended that appropriate precautions be taken during agricultural operations, and also by those participating in recreational visits to forested areas.
(ProMED 8/18/09)

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Russia (Volgograd): Two cases, including one fatality of Crimean-Congo hemorrhagic fever
As of 5 Aug 2009, there have been two cases of Crimean-Congo hemorrhagic fever (CCHF) in Volgograd, one of which resulted in death. The regional Rospotrebnadzor laboratory conducted 12 PCR tests on human specimens and found two of them were positive.

There were 212 cases of CCHF in the South Federal Okrug of Russia in 2008. Investigators at the Volgograd Centre for Hygiene and Epidemiology collected a total of 4856 ticks. So far in 2009, 846 samples of ticks have been tested for CCHF virus antigen, of which nine samples tested positive (1 percent). Of 585 samples of ticks tested in 2008, 3.2 per cent tested positive.
(ProMED 8/15/09)

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In Ontario, confirmed cases fell from 1870 when the MNR introduced a rabies vaccine baiting program in 1989 to 79 in 2008, a 95.8 percent decrease. "With this bait and the technology that we're using, we feel that elimination is a possibility, so we'll work toward a number of zero," said Dennis Donovan, the MNR's rabies unit co-ordinator.

Bats carrying the virus will continue to fly into Ontario, he said, but the MNR's goal is to eliminate rabies in terrestrial mammals such as fox, raccoon and skunk. 2 years without a confirmed case are required for the World Health Organization to declare the province "rabies free," Donovan said.
(ProMED 8/18/09)

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Mexico: Outbreak of brucellosis prompts warnings to avoid unpasteurized dairy products
Given the spread of an outbreak of brucellosis in the area since the beginning of August 2009, the head of the local health jurisdiction VII, Joel Martinez Mendez, called on the population of Leon to avoid the consumption of unpasteurized dairy products, mainly those derived from goat's milk.

To date, 28 cases have been reported in the locality, although only 18 were confirmed. This makes Leon the third city with the most cases in 2009, after Guanajuato with 136 cases and Romita with 110 cases.

Martinez Mendez noted that brucellosis bacteria can remain living in refrigerated contaminated milk for up to 10 days, in Roquefort cheese for two months, and in refrigerated butter for four months. In the environment the bacteria can survive in water for 10 to 70 days and in the dust or soil for up to 10 weeks.
(ProMED 8/17/09)

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USA (Alaska): Rare bacterial infection confirmed in 2 Fairbanks residents
Two residents of Fairbanks, Alaska have been diagnosed with tularemia, a potentially fatal bacterial infection more commonly found in animals. Alaska Department of Fish and Game veterinarian Kimberlee Beckmen learned of the outbreak from state public health authorities during the first week of Aug 2009.

The disease can be transmitted to humans from snowshoe hares, and the hare population has been high in the interior. It's unclear how the Fairbanks residents contracted it. Beckmen says people are usually infected through the skin by handling sick hares, but they can also get it when bitten by ticks, flies, or mosquitoes that fed on sick hares. A Fish and Game spokeswoman says the Fairbanks patients were treated with antibiotics and are doing well.
(ProMED 8/10/09)

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- WHO
Influenza A/H1N1: http://www.who.int/csr/disease/swineflu/en/index.html
Influenza A/H1N1 frequently asked questions: http://www.who.int/csr/swine_flu/swine_flu_faq_26april.pdf
Pandemic Influenza Preparedness and Response - A WHO Guidance Document http://www.who.int/csr/disease/influenza/pipguidance2009/en/index.html
International Health Regulations (IHR) at http://www.who.int/ihr/en
/index.html.

- WHO regional offices
Africa: http://www.afro.who.int/
Americas: http://new.paho.org/hq/index.php?option=com_content&task=blogcategory&id=805&Itemid=569
Eastern Mediterranean: http://www.emro.who.int/csr/h1n1/
Europe: http://www.euro.who.int/influenza/ah1n1
South-East: http://www.searo.who.int/EN/Section10/Section2562.htm
Western Pacific: http://www.wpro.who.int/health_topics/h1n1/

- North America
US CDC: http://www.cdc.gov/flu/swine/investigation.htm
US pandemic emergency plan: www.pandemicflu.gov
MOH Mexico: http://portal.salud.gob.mx/index_eng.html
PHAC: http://www.phac-aspc.gc.ca/media/nr-rp/index-eng.php

- Other useful sources
CIDRAP: Influenza A/H1N1 page: http://www.cidrap.umn.edu/cidrap/content/influenza/swineflu/biofacts/swinefluoverview.html
ProMED: http://www.promed.org

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AVIAN INFLUENZA
- UN: http://www.undp.org/mdtf/influenza/overview.shtml UNDP’s web site for information on fund management and administrative services and includes the website of the Central Fund for Influenza Action. This site also includes a list of useful links.
- WHO: http://www.who.int/csr/disease/avian_influenza/en/index.html The (interim) Influenza Virus Tracking System can be accessed at: www.who.int/fluvirus_tracker.
- UN FAO: http://www.fao.org/avianflu/en/index.html. View the latest avian influenza outbreak maps, upcoming events, and key documents on avian influenza.
- OIE: http://www.oie.int/eng/info_ev/en_AI_avianinfluenza.htm. Link to the Communication Portal gives latest facts, updates, timeline, and more.
- US CDC: Visit "Pandemic Influenza Preparedness Tools for Professionals" at: http://www.cdc.gov/flu/pandemic/preparednesstools.htm. This site contains resources to help hospital administrators and state and local health officials prepare for the next influenza pandemic.
- The US government’s website for pandemic/avian flu: http://www.pandemicflu.gov/. View archived Webcasts on influenza pandemic planning.
- CIDRAP: http://www.cidrap.umn.edu/ Access their Swine Influenza website at http://www.cidrap.umn.edu/cidrap/content/influenza/swineflu/index.html.
- PAHO: http://www.paho.org/English/AD/DPC/CD/influenza.htm Link to the Avian Influenza Portal at: http://influenza.bvsalud.org/php/index.php?lang=en. The Virtual Health Library’s Portal is a developing project for the operation of product networks and information services related to avian influenza.
- US National Wildlife Health Center: http://www.nwhc.usgs.gov/disease_information/avian_influenza/index.jsp Read about the latest news on H5N1 in wild birds and poultry.

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DENGUE
Mexico
On 4 Aug 2009, the Mexican government urged its citizens to combat dengue fever, a mosquito-borne tropical virus infection that causes muscle pain, internal bleeding, and death. Mexican health minister Jose Angel Cordoba Villalobos urged the public to avoid standing water in abandoned cars and garbage, which attracts mosquitoes, and to keep houses clean. He also asked Mexicans to report to the health authorities immediately if they show any symptoms of dengue.

The disease is threatening the lives of thousands of Mexicans. Some 8895 cases of dengue had been confirmed by 2 Aug 2009, compared with a total of 10,400 cases registered in 2008, Cordoba Villalobos stated.

Many state authorities have issued virus alerts to local residents, including Colima, Guanajuato, Guerrero, Hidalgo, Puebla, San Luis Potosi, and the state of Mexico. Sanitary barriers were set up in Gorda mountain range in Queretaro State. Residents of several other states have launched yard and roof cleaning campaigns to combat the disease.
(ProMED 8/11/09)

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Novel influenza A (H1N1) virus infection continues to cause illness and death among persons worldwide. Immunosuppressed patients with influenza virus infection can shed virus for prolonged periods, increasing the chances for development of drug resistance. On August 6, 2009, CDC detected evidence of resistance to the antiviral medication oseltamivir in two severely immunosuppressed patients with novel influenza A (H1N1) virus infection in Seattle, Washington. The two patients were treated in two different hospitals, and their cases were not epidemiologically linked. Both were being treated with oseltamivir for novel influenza A (H1N1) virus infection and had prolonged viral shedding. In both patients, the virus was documented as initially susceptible to oseltamivir, and resistance developed subsequently during treatment with the drug. Testing of viral RNA from both patients by pyrosequencing detected a mutation that results in a histidine-to-tyrosine substitution at position 275 (H275Y) in the neuraminidase, known to be associated with oseltamivir resistance. The results were confirmed by pyrosequencing, sequencing of the neuraminidase gene, and neuraminidase inhibition testing of virus isolates on August 11. One patient's symptoms resolved after treatment with oseltamivir, and the other patient was receiving treatment with zanamivir and ribavirin as of August 13. An investigation of health-care personnel (HCP) contacts and other close contacts revealed no evidence of virus transmission. This report summarizes the case histories and resulting investigations and highlights the importance of 1) close monitoring for antiviral drug resistance among immunosuppressed patients receiving treatment for novel influenza A (H1N1) virus infection and 2) the implications for infection control. (Excerpt with references removed.)

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Prescription of anti-influenza drugs for healthy adults: a systematic review and meta-analysis
Burch J et al. Lancet Infect Dis. Sep 2009; 9(9): 537-545. Available at http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(09)70199-9/abstract.

Summary
In publicly funded health systems with finite resources, management decisions are based on assessments of clinical effectiveness and cost-effectiveness. The UK National Institute for Health and Clinical Excellence commissioned a systematic review to inform their 2009 update to guidance on the use of antiviral drugs for the treatment of influenza. We searched databases for studies of the use of neuraminidase inhibitors for the treatment of seasonal influenza. We present the results for healthy adults (ie, adults without known comorbidities) and people at-risk of influenza-related complications. There was an overall reduction in the median time to symptom alleviation in healthy adults by 0.57 days (95% CI −1.07 to −0.08; p=0.02; 2701 individuals) with zanamivir, and 0.55 days (95% CI −0.96 to −0.14; p=0.008; 1410 individuals) with oseltamivir. In those at risk, the median time to symptom alleviation was reduced by 0.98 days (95% CI −1.84 to −0.11; p=0.03; 1252 individuals) with zanamivir, and 0.74 days (95% CI −1.51 to 0.02; p=0.06; 1472 individuals) with oseltamivir. Little information was available on the incidence of complications. In view of the advantages and disadvantages of different management strategies for controlling seasonal influenza in healthy adults recommending the use of antiviral drugs for the treatment of people presenting with symptoms is unlikely to be the most appropriate course of action.

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Safety and Immunogenicity of a Novel Influenza Subunit Vaccine Produced in Mammalian Cell Culture
Szymczakiewicz-Multanowska A et al. J Infect Dis. 15 Sep 2009; 200: 841-848. Available at http://www.journals.uchicago.edu/doi/abs/10.1086/605505.

Abstract
Background. Immunization remains the best prevention strategy for influenza, but production constraints for egg-based influenza vaccines have prompted the development of innovative cell culture manufacturing processes. Here, we describe a novel cell culture–derived influenza vaccine (CCIV) produced in Madin-Darby canine kidney cells.

Methods. This phase 3, observer-blind, randomized, multicenter study in Poland compared the immunogenicity of a CCIV and a conventional egg-based vaccine. Participants, stratified by age (adults 18–60 years, n=1300; elderly persons >= 61 years, n=1354), received a single intramuscular vaccination. Immunogenicity was assessed 21 days later by hemagglutination inhibition assay. Reactogenicity was assessed using self-completed diary cards.

Results. The immunogenicity of CCIV was noninferior to that of the conventional vaccine for all 3 vaccine strains in both age groups, regardless of underlying health status. Both vaccines fulfilled European Union registration criteria and were well tolerated, with similar incidences of solicited local and systemic reactions in both age groups; the only significant difference was an increased frequency of mild or moderate pain with CCIV than the conventional vaccine among adult (22% vs 17%; p<0.05) and elderly (9% vs 5%; p<0.001) vaccinees.

Conclusions. CCIV was well tolerated and highly immunogenic in adults 18 years of age or older. Cell culture may offer greater flexibility of supply during periods of high demand for both seasonal and pandemic vaccines.

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Subunit Influenza Vaccines Produced from Cell Culture or in Embryonated Chicken Eggs: Comparison of Safety, Reactogenicity, and Immunogenicity
Reisinger KS et al. J Infect Dis. 15 Sep 2009; 200: 849-857. Available at http://www.journals.uchicago.edu/doi/abs/10.1086/605506.

Abstract
Background. This study assessed the safety, reactogenicity, and immunogenicity of an injectable cell culture–derived influenza vaccine (CCIV), compared with those of an injectable egg‐based trivalent inactivated influenza vaccine (TIV).

Methods. Adult subjects (n=613; 18 to <50 years of age) were randomized (1:1) to receive either CCIV or TIV. The safety and reactogenicity of the 2 vaccines were assessed on the basis of solicited indicators and other adverse events (AEs) within 7 days of vaccination. All serious AEs and those AEs resulting in withdrawal were recorded throughout the study. Antibody titers were determined by the hemagglutination inhibition assay, using egg‐ and cell‐derived antigens. Immunogenicity was assessed on the basis of the ratio of postvaccination (day 22) geometric mean titers (GMTs) between the 2 vaccines, seroprotection rates, and seroconversion rates.

Results. There was no clinically relevant difference between the safety and reactogenicity profiles of the 2 vaccines. The immunogenicity of CCIV was demonstrated to be noninferior to that of TIV on the basis of the ratio of postvaccination GMTs between the 2 vaccines. GMTs, seroprotection rates, and seroconversion rates were comparable between the 2 vaccines.

Conclusions. The safety, reactogenicity, and immunogenicity of the CCIV and the egg-based TIV are comparable.

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Original Antigenic Sin Responses to Influenza Viruses
Kim JH et al. J Immunol. 31 Jul 2009 (early online publication). Available at http://www.jimmunol.org/cgi/content/abstract/jimmunol.0900398v1.

Most immune responses follow Burnet's rule in that Ag recruits specific lymphocytes from a large repertoire and induces them to proliferate and differentiate into effector cells. However, the phenomenon of "original antigenic sin" stands out as a paradox to Burnet's rule of B cell engagement. Humans, upon infection with a novel influenza strain, produce Abs against older viral strains at the expense of responses to novel, protective antigenic determinants. This exacerbates the severity of the current infection. This blind spot of the immune system and the redirection of responses to the "original Ag" rather than to novel epitopes were described fifty years ago. Recent reports have questioned the existence of this phenomenon. Hence, we revisited this issue to determine the extent to which original antigenic sin is induced by variant influenza viruses. Using two related strains of influenza A virus, we show that original antigenic sin leads to a significant decrease in development of protective immunity and recall responses to the second virus. In addition, we show that sequential infection of mice with two live influenza virus strains leads to almost exclusive Ab responses to the first viral strain, suggesting that original antigenic sin could be a potential strategy by which variant influenza viruses subvert the immune system.

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Contents include:
Global leprosy situation, 2009

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Preparing for the Flu: A Communication Toolkit for Businesses and Employers
Issued by the US Department of Health and Human Services.
Available at http://www.flu.gov/plan/workplaceplanning/toolkit.html

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Technical Report on CDC Guidance for Responses to Influenza for Institutions of Higher Education during the 2009-2010 Academic Year
US Centers for Disease Control and Prevention document released 20 Aug 2009.
Available at http://www.cdc.gov/h1n1flu/institutions/guidance/technical.htm.

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CDC Guidance for Responses to Influenza for Institutions of Higher Education during the 2009-2010 Academic Year
US for Disease Control and Prevention document released 20 Aug 2009.
Available at http://www.cdc.gov/h1n1flu/institutions/guidance/.

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