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Vol. XII, No. 17 ~ EINet News Briefs ~ Aug 21, 2009
*****A free service of the APEC Emerging Infections Network*****
APEC EINet News Briefs offers the latest news, journal articles, and notifications for emerging infections affecting the APEC member economies. It was created to foster transparency, communication, and collaboration in emerging infectious diseases among health professionals, international business and commerce leaders, and policy makers in the Asia-Pacific region.
In this edition:
1. Influenza News
- Weekly APEC update of pandemic influenza (H1N1) 2009
- Cumulative number of human cases of avian influenza A/(H5N1)
- Global: 'Original antigenic sin': A threat to H1N1 vaccine effectiveness?
- Global: Researchers suggest osteoporosis drugs may have antiviral benefits
- UK: Government rejects experts’ advice regarding widespread use of Tamiflu
- UK: Agency says Tamiflu plus warfarin may increase stroke risk
- Australia: Second piggery quarantined due to pandemic influenza H1N1
- Australia: Young man survives near-fatal case of pandemic H1N1 with help of IV zanamivir
- China: Firm claims good results in pandemic influenza H1N1 vaccine clinical trial
- Latin America: Deaths due to pandemic influenza H1N1 top 1300
- USA: 41 more pandemic H1N1 influenza related deaths
- USA: Federal officials offer new pandemic H1N1 guidance for businesses
- USA (Massachusetts): Communities of color disproportionately affected by pandemic H1N1 influenza
- USA (New York): Mandates health workers obtain influenza vaccinations
- Egypt: Protests against travel ban aimed to curb spread of pandemic H1N1 virus
2. Infectious Disease News
- Australia: Airline listeria outbreak linked to chicken
- China (Heilongjiang): Hemorrhagic fever outbreak ails 7
- Russia (Novosibirsk): Over 500 people hospitalized due to tick bites
- Russia (Udmurtia): Hemorrhagic fever with renal syndrome situation continues to be unstable
- Russia (Volgograd): Two cases, including one fatality of Crimean-Congo hemorrhagic fever
- Canada (Ontario): Confirmed rabies cases in Grey-Bruce continue to decline
- Mexico: Outbreak of brucellosis prompts warnings to avoid unpasteurized dairy products
- USA (Alaska): Rare bacterial infection confirmed in 2 Fairbanks residents
- INFLUENZA A/H1N1
- AVIAN INFLUENZA
- Oseltamivir-Resistant Novel Influenza A (H1N1) Virus Infection in Two Immunosuppressed Patients--Seattle, Washington, 2009
- Prescription of anti-influenza drugs for healthy adults: a systematic review and meta-analysis
- Safety and Immunogenicity of a Novel Influenza Subunit Vaccine Produced in Mammalian Cell Culture
- Subunit Influenza Vaccines Produced from Cell Culture or in Embryonated Chicken Eggs: Comparison of Safety, Reactogenicity, and Immunogenicity
- Original Antigenic Sin Responses to Influenza Viruses
- Weekly Epidemiological Record Bulletin
- Preparing for the Flu: A Communication Toolkit for Businesses and Employers
- Technical Report on CDC Guidance for Responses to Influenza for Institutions of Higher Education during the 2009-2010 Academic Year
- CDC Guidance for Responses to Influenza for Institutions of Higher Education during the 2009-2010 Academic Year
1. Influenza News
Weekly APEC update of pandemic influenza (H1N1) 2009
Hong Kong reported its second case of Tamiflu resistant pandemic H1N1 virus. Australia expects first doses of pandemic H1N1 influenza vaccine to be available next week [24 Aug 2009]. November 2009 is the anticipated immunization start date for Canada. The initial shipment should consist of 10-15 million doses. China’s education and health ministries have ordered strong measures to curb the spread of the pandemic H1N1flu virus when schools reopen including postponing the start of the school year in areas with high infection rates. Schools have also been advised not to hold large gatherings and to reduce class sizes. Meanwhile, two school districts in Quebec, Canada are keeping pregnant teachers at home this fall to reduce their risk of severe complications if they get sick with pandemic H1N1 flu.
(CIDRAP 8/19/09, 8/17/09, 8/14/09)
***For data on human cases of avian influenza prior to 2009, go to:
Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 438 (262).
Avian influenza age distribution data from WHO/WPRO:
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):
Global: 'Original antigenic sin': A threat to H1N1 vaccine effectiveness?
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.
Global: Researchers suggest osteoporosis drugs may have antiviral benefits
Full Reuters story available at http://www.reuters.com/article/asiaCrisis/idUSHKG233114.
UK: Government rejects experts’ advice regarding widespread use of Tamiflu
The British government rejected advice from its expert advisers on influenza pandemic (H1N1) 2009 virus, who said there was no need for the widespread use of Tamiflu and suggested that the public should simply be told to take paracetamol. An independent panel set up by the Department of Health warned ministers that plans to make the stockpiled drug widely available could do more harm than good, by helping the flu virus to develop resistance to the drug. But ministers pressed ahead with a policy of mass prescription, fearing the public would not tolerate being told that the millions of doses of Tamiflu held by the state could not be used during a pandemic, one of the committee members said.
"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.
UK: Agency says Tamiflu plus warfarin may increase stroke risk
Australia: Second piggery quarantined due to pandemic influenza H1N1
A second Australian piggery was placed in quarantine due to pandemic influenza H1N1 on 19 Aug 2009 as the number of human deaths in the country attributed to the virus reached 121. Authorities ordered a biosecurity lockdown at the piggery in Victoria state amid concerns the virus could mutate and return to humans in a more deadly form. Another piggery in New South Wales state has been quarantined since late July 2009, although the state government said most of the animals had recovered from the disease.
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.
Australia: Young man survives near-fatal case of pandemic H1N1 with help of IV zanamivir
China: Firm claims good results in pandemic influenza H1N1 vaccine clinical trial
Latin America: Deaths due to pandemic influenza H1N1 top 1300
Deaths from pandemic H1N1 flu in Latin America, the world's hardest-hit region, have reached 1,303, more than 70% of the global total of 1,799 listed by the World Health Organization. Argentina has had 404 deaths, the second-highest toll after the United States' 477, and Brazil has reported 368. Trailing Brazil are Mexico, with 164 deaths, Chile with 105 and Peru at 62.
USA: 41 more pandemic H1N1 influenza related deaths
USA: Federal officials offer new pandemic H1N1 guidance for businesses
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.
USA (Massachusetts): Communities of color disproportionately affected by pandemic H1N1 influenza
USA (New York): Mandates health workers obtain influenza vaccinations
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.”
Egypt: Protests against travel ban aimed to curb spread of pandemic H1N1 virus
About 300 people staged a protest at Cairo's airport on 16 Aug 2009 to oppose an Egyptian government restriction that bars them from traveling to Mecca on pilgrimage, the Associated Press reported. Airport security dispersed the crowd. The travel ban is intended to slow the spread of the pandemic H1N1 virus. Only travelers between ages 25 and 65, a group generally thought to be at lower risk for flu, are allowed to make the trip to Mecca.
2. Infectious Disease News
Australia: Airline listeria outbreak linked to chicken
A food processing plant in Wollongong has been identified as the source of a listeria food poisoning outbreak on Virgin Blue flights in July 2009. Food Authority of Queensland tests revealed the listeria bacteria (Listeria monocytogenes) came from cooked, diced chicken supplied by GMI Food Wholesalers Pty Ltd, which trades as Australian Poultry and Food Wholesalers, Primary Industries Minister Ian Macdonald said 19 Aug 2009. The company operates a food processing plant on Auburn Street in Wollongong.
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.
China (Heilongjiang): Hemorrhagic fever outbreak ails 7
Russia (Novosibirsk): Over 500 people hospitalized due to tick bites
Russia (Udmurtia): Hemorrhagic fever with renal syndrome situation continues to be unstable
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.
Russia (Volgograd): Two cases, including one fatality of Crimean-Congo hemorrhagic fever
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.
Canada (Ontario): Confirmed rabies cases in Grey-Bruce continue to decline
The Ministry of Natural Resources (MNR) forecasts that rabies cases will continue to drop for the next 3 to 5 years, the province's timeline to virtually eliminate the viral disease in Ontario, Canada. A total of four skunks and one fox have tested positive for rabies so far in 2009 in Grey-Bruce, according the Grey Bruce Health Unit. Year-to-year cases fell 66 percent from 2006 to 2008.
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.
Mexico: Outbreak of brucellosis prompts warnings to avoid unpasteurized dairy products
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.
USA (Alaska): Rare bacterial infection confirmed in 2 Fairbanks residents
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.
The following websites provide the most current information, surveillance, and guidance.
- WHO regional offices
- North America
- Other useful sources
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.
Oseltamivir-Resistant Novel Influenza A (H1N1) Virus Infection in Two Immunosuppressed Patients--Seattle, Washington, 2009
US Centers for Disease Control & Prevention. MMWR. 14 Aug 2009; 58(Dispatch): 1-4. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm58d0814a1.htm?s_cid=mm58d0814a1_e.
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.)
Prescription of anti-influenza drugs for healthy adults: a systematic review and meta-analysis
Safety and Immunogenicity of a Novel Influenza Subunit Vaccine Produced in Mammalian Cell Culture
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.
Subunit Influenza Vaccines Produced from Cell Culture or in Embryonated Chicken Eggs: Comparison of Safety, Reactogenicity, and Immunogenicity
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.
Original Antigenic Sin Responses to Influenza Viruses
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.
Weekly Epidemiological Record Bulletin
WHO. 14 Aug 2009; 84(33): 333-340. Available at http://www.who.int/wer.
Preparing for the Flu: A Communication Toolkit for Businesses and Employers
Technical Report on CDC Guidance for Responses to Influenza for Institutions of Higher Education during the 2009-2010 Academic Year
CDC Guidance for Responses to Influenza for Institutions of Higher Education during the 2009-2010 Academic Year