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Vol. XII, No. 16 ~ EINet News Briefs ~ Aug 07, 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: WHO says pandemic influenza 2009 H1N1 has reached 168 countries
- Global: WHO lists warning signs for severe pandemic influenza 2009 H1N1 disease
- Global: WHO believes 2 billion people could catch pandemic influenza 2009 H1N1
- Global: WHO says pandemic influenza H1N1 vaccine process won't sacrifice safety
- Global: Two health care workers die of pandemic influenza 2009 H1N1 infection
- Australia (New South Wales): Pandemic influenza 2009 H1N1 confirmed in swine
- Chinese Taipei, Hong Kong: Influenza H3N2 circulating with pandemic H1N1 2009 virus
- Indonesia: Girl hospitalized with suspected avian influenza H5N1
- Russia: Official warns against travel to the UK due to pandemic influenza 2009 H1N1 outbreaks
- Argentina: Pace of pandemic influenza 2009 H1N1 has slowed
- North America: PAHO rejects report of resistant pandemic H1N1 cases on US-Mexico border
- USA: Some experts call for more use of pneumococcal vaccine in pandemic influenza H1N1 battle

2. Infectious Disease News
- China (Qinghai): Outbreak of pneumonic plague kills three, thousands quarantined
- Russia (Chelyabinsk): Update of tick-borne encephalitis in 2009
- Singapore: 3 clusters of malaria under investigation, suspected local transmission
- USA: Salmonellosis outbreak prompts ground beef recall
- USA (Minnesota): Cases of serious tick-borne disease in 2008 and 2009
- USA (Utah): Rabid bats attack girls in Weber County

3. Updates
- INFLUENZA A/H1N1
- AVIAN INFLUENZA
- DENGUE

4. Articles
- Public Health and Medical Responses to the 1957-58 Influenza Pandemic
- Evaluation of Rapid Influenza Diagnostic Tests for Detection of Novel Influenza A (H1N1) Virus--United States, 2009
- Facemasks and Hand Hygiene to Prevent Influenza Transmission in Households
- Safety and Efficacy of Extended-Duration Antiviral Chemoprophylaxis Against Pandemic and Seasonal Influenza
- Supply and safety issues surrounding an H1N1 vaccine
- Zanamivir-Resistant Influenza Viruses with a Novel Neuraminidase Mutation
- Artemisinin Resistance in Plasmodium falciparum Malaria
- Laboratory-Acquired Vaccinia Virus Infection--Virginia, 2008

5. Notifications
- US Centers for Disease Control and Prevention tools and resources updated
- Weekly Epidemiological Record Bulletin
- International Swine Flu Conference


1. Influenza News

Global
Weekly APEC update of pandemic influenza (H1N1) 2009
Viet Nam reports its first pandemic H1N1 fatality. The US CDC's flu surveillance report for the week ending 25 Jul 2009 says that novel H1N1 activity continued to drop for the fifth consecutive week, with only four states and Puerto Rico reporting widespread activity, down from seven states the week before. CDC reported a total of 5514 hospitalizations due to novel H1N1 infection. China's health ministry is canceling summer camps in areas where novel H1N1 outbreaks are occurring. The action follows reports of more than 120 illnesses in summer camps in Beijing and in Guangzhou in southern China.
(ProMED 8/5/09; CIDRAP 8/4/09)

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Cumulative number of human cases of avian influenza A/(H5N1)
Economy / Cases (Deaths)
2009
China/ 7 (4)
Egypt/ 27 (4)
Viet Nam/ 4 (4)
Total/ 41 (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: 436 (262).
(WHO 7/1/09 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: WHO says pandemic influenza 2009 H1N1 has reached 168 countries
The World Health Organization (WHO) said on 4 Aug that 168 countries and territories on all continents have now had cases and that the new virus increasingly dominates the flu landscape. WHO said 13 countries and jurisdictions reported 3,548 "detections" of the pandemic virus to WHO in the week of 20-26 Jul 2009. The new virus accounted for an average of 71% of all flu viruses identified in those countries--66% in the northern hemisphere and 89% in the southern hemisphere.

Hong Kong led the list of countries reporting new detections with 1,788, followed by Australia with 834 and Italy with 600. The number of deaths among known H1N1 cases reached 1,154 as of 31 Jul 2009, up from 816 on Jul 27, the agency reported. While noting that the number of confirmed cases understates the real numbers, the agency said the confirmed case tally reached 162,380 as of 31 Jul 2009, compared with 134,503 on 27 Jul 2009.

Six oseltamivir-resistant H1N1 cases have been detected so far, including three in Japan and one each in Denmark, Hong Kong, and Canada, the WHO reported. All but one of the patients had been treated with the antiviral, and all have recovered. All the resistant viruses carried the characteristic resistance-linked mutation at position 274/275.

The statement lists "qualitative indicators" of the H1N1 situation for the week of 13-19 Jul 2009. It says that most countries in North and South America had widespread activity, whereas in Europe only the United Kingdom and Portugal had widespread activity. Several other European countries had localized or regional outbreaks. Most Asian countries reporting cases had only localized outbreaks, the agency said.

The report lists the following case counts and deaths tolls for WHO regions as of 31 Jul 2009: the Americas, 98,242 cases and 1,008 deaths; the Western Pacific, 26,661 and 39; Europe, 26,089 and 41; Southeast Asia, 9,858 and 65; the Eastern Mediterranean, 1,301 and 1, and Arica, 229 cases with no deaths. The latest countries to report confirmed cases are Azerbaijan, Gabon, Grenada, Kazakhstan, Moldova, Monaco, Nauru, Swaziland, and Suriname, the WHO said.
(CIDRAP 8/4/09)

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Global: WHO lists warning signs for severe pandemic influenza 2009 H1N1 disease
On 31 Jul 2009, the World Health Organization (WHO) issued a list of warning signs of possible severe disease in H1N1 flu patients, while adding its voice to the recent warnings about the virus's threat to pregnant women. WHO said signs that can signal a progression to severe disease include shortness of breath, difficulty breathing, turning blue, bloody or colored sputum, chest pain, altered mental status, high fever lasting more than three days, and low blood pressure. In addition, particular danger signs in children include fast or difficult breathing, lack of alertness, difficulty in waking up, and little or no desire to play, the agency said.

Because a patient's condition can worsen very quickly, medical attention should be sought when any of the warning signs appear, the WHO advised. The agency noted that most patients continue to have mild symptoms and recover fully within a week, but a few people, usually younger than 50, rapidly progress to severe and sometimes fatal illness. "No factors that can predict this pattern of severe disease have yet been identified, though studies are under way," the statement said.

Regarding pregnant women, the WHO noted a US study published this week in The Lancet that showed an increased risk of severe or fatal H1N1 disease in this group. Several other countries also have noted an increased risk for pregnant women and a higher risk of fetal death or spontaneous abortion, the agency said. "WHO strongly recommends that, in areas where infection with the H1N1 virus is widespread, pregnant women, and the clinicians treating them, be alert to symptoms of influenza-like illness," the statement said. The agency said pregnant women should be treated with oseltamivir as soon as possible after symptom onset and should be a priority group for immunization.

The WHO said monitoring of viruses from multiple outbreaks has revealed no evidence of a change in the virus's ability to spread or cause severe illness.
(CIDRAP 7/31/09)

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Global: WHO believes 2 billion people could catch pandemic influenza 2009 H1N1
Health officials raised the alarm about a strain of pandemic H1N1 that is resistant to the Tamiflu treatment as the virus claimed more lives on 4 Aug 2009, with Viet Nam reporting its first fatal case. India and South Africa both reported their first cases of the A(H1N1) virus late 3 Aug 2009. Maria Teresa Cerqueira, head of the Pan-American Health Organization office in La Jolla, California, said a Tamiflu-resistant mutation of pandemic influenza A(H1N1) had been found around the US-Mexico border in El Paso and close to McAllen, Texas. Experts discussed 3 Aug 2009 responses to the outbreak, and warned that resistant strains were likely emerging because of overuse of antivirals like Tamiflu. "In the United States Tamiflu is sold with a prescription, but in Mexico and Canada it is sold freely and taken at the first sneeze. Then, when it is really needed, it doesn't work," said Cerqueira. Cases of pandemic A(H1N1) that were resistant to the anti-viral medicine have now been found in the US, Canada, Denmark, Hong Kong and Japan.

As the northern hemisphere autumn approaches, WHO is working with drug companies to ensure vaccines to cope both with pandemic H1N1 and seasonal flu will be available. Leading flu vaccine makers include Sanofi-Aventis, Novartis , Baxter, GlaxoSmithKline and Solvay.

Novartis has started human testing of pandemic H1N1 flu vaccine candidates while Sanofi-Aventis, the world leader in flu shots, will commence within days, company officials said on 4 Aug 2009. GlaxoSmithKline said it would initiate clinical studies later in August 2009. Healthcare officials are relying on a vaccine to contain the spread of disease, providing a potential sales windfall for those companies that are able to deliver quickly and in large volume.

Australia's CSL has so far been the fastest commercial operator, after starting its first clinical trials in Australia two weeks ago. Others are catching up. Benoit Rungeard, product communications director for Sanofi Pasteur, the vaccines division of the French drug maker, said his company would start "in the coming days or next week." Althoff said Novartis was conducting its clinical trials in a number of countries, including the US, Britain and Germany, and was testing both single and booster, or repeat, doses of vaccines. Novartis, in common with other manufacturers, will also compare vaccines with and without adjuvants--ingredients that boost the immune system response. AstraZeneca, whose MedImmune unit makes smaller amounts of a flu vaccine that is sprayed into the nose rather than injected, said it would start clinical trials in the US around 17 Aug 2009.

Meanwhile, a Taiwanese biotech company on 4 Aug 2009 started mass production of a pandemic H1N1 flu vaccine before even completing clinical trials, in a bid to get a jump before the start of the winter flu season. Adimmune Corp, the island's only human vaccine manufacturer, said it was starting production at its plant in central Taichung. The company is due to deliver 5 million doses of A(H1N1) influenza vaccine before the end of October 2009, according to the purchase contract it has signed with the government, said deputy CEO and president Ignatius Wei. The company says it has completed some animal trials of the vaccine, but will only begin human trials in Sep 2009--sparking criticism about the risks of manufacturing an as-yet unproven product. But Huang Li-min of the National Taiwan University Hospital who will oversee the human trials says Adimmune is taking a calculated risk. "They have to do so. . .they are racing against time," Huang said, referring to the upcoming start of flu season.
(ProMED 8/5/09)

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Global: WHO says pandemic influenza H1N1 vaccine process won't sacrifice safety
The World Health Organization (WHO) said 6 Aug 2009 that the fast-tracking of vaccines for pandemic H1N1 influenza won't compromise safety, while acknowledging that clinical data will be limited when the first doses are administered. "The public needs to be reassured that regulatory procedures in place for the licensing of pandemic vaccines, including procedures for expediting regulatory approval, are rigorous and do not compromise safety or quality controls," the agency said.

WHO's Dr. Marie-Paule Kieny said the first results of H1N1 vaccine clinical trials are expected in the first half of Sep 2009, and some countries may start using the vaccines the same month, if their regulatory agencies approve. Trials are under way in China, Australia, the United Kingdom, Germany, and the US, she said. The trials are mainly designed to determine whether one or two doses of vaccine will be needed to induce an immune response, while providing some safety data.

Kieny, director of the WHO Initiative for Vaccine Research, noted that the US may treat pandemic H1N1 vaccines the same way it handles the switching of viral strains in seasonal flu vaccines, which does not require clinical trial data for licensing. European regulators do require a clinical trial for a strain change in a seasonal vaccine, she said, but manufacturers that have previously filed data for a "mock-up" pandemic vaccine may get approval for an H1N1 vaccine before submitting clinical trial data.

WHO said some media reports have voiced concern about the safety of H1N1 vaccines. The agency said vaccines need to be made available quickly and in large quantities to fight the pandemic. That didn't happen in the 1957 and 1968 pandemics, when vaccines arrived too late to be of much help during the height of the outbreaks.

Better yields expected
Kieny said a better-yielding vaccine seed strain may be on the way to replace the strains now in use, which have yielded disappointing results. The WHO's collaborating centers have been working to develop strains that grow better in eggs, "and the latest result we've heard as of this week is that at least one of the strains seems to be promising and seems to get equivalent yields to the ones the manufacturers have for seasonal vaccines," she said. "It seems we've found a way to get around this problem."

She gave no details on where the improved strain was developed, but a Canadian Press report published 5 Aug 2009 said it was produced by Britain's National Institute for Biological Standards and Controls. Kieny declined to make any predictions about global H1N1 vaccine production capacity. She said an earlier projection of up to 94 million doses per week was a best-case scenario, and the WHO needs more data before making any new predictions.

Regulatory pathways
WHO said that some pandemic vaccines are not regarded as entirely new, because they build on seasonal vaccine technology, established testing procedures, and a large body of safety data. "In such cases, approval procedures are similar to those applied to 'strain changes' made each year when seasonal vaccines are modified to match circulating viruses in the northern and southern hemispheres."

Kieny noted that the US Food and Drug Administration expects to use this approach with H1N1 vaccines based on the same technology and processes as seasonal vaccines. However, that won't be the case with vaccines containing dose-sparing adjuvants, she noted. Because the US, unlike Europe, has never licensed an adjuvanted flu vaccine, US regulators "will request to review full clinical development," she said. The US government has ordered millions of doses of two different adjuvants, and officials have said that adjuvanted vaccines could be used under a special emergency authorization.

The European Union requires small clinical trials for strain changes in seasonal flu vaccines, Kieny said. But she noted that in view of the threat of H5N1 avian flu, the EU set up a process allowing manufacturers to develop prototype H5N1 vaccines and submit data, with the understanding that when a pandemic emerged, the pandemic strain could be substituted for the prototype strain. Manufacturers that filed mockup vaccine data "can present to the regulatory agency all the documentation for the H1N1 vaccine, and as previously agreed already in 2007, obtain a registration without clinical trials," she said. However, she added that all manufacturers will conduct clinical trials and submit the data as soon as possible, with the earliest expected in September 2009.

Safety issues inevitable
The agency said safety issues will inevitably arise during mass vaccination efforts. "For example, adverse events too rare to show up even in a large clinical trial may become apparent when very large numbers of people receive a pandemic vaccine." Such was the case in the swine flu vaccination campaign in 1976, when several hundred people, out of more than 40 million vaccinated, suffered Guillain-Barre syndrome. But Kieny said such events are less likely today: "The vaccines we have now are much purer and the quality control and lab testing on today's vaccines is much better than it was 30 years ago."

Kieny said WHO has no special concerns about the safety of adjuvanted H1N1 vaccines. "We've reviewed the safety of adjuvanted vaccines as they've been tested for H5N1, and more than 40 million doses of adjuvanted vaccine have been used in Europe already," she said. But she also said there has been no experience in the use of adjuvanted flu vaccines in pregnant women, who are a priority group for H1N1 vaccination. The WHO's Strategic Advisory Group of Experts (SAGE), she said, recommended in July 2009 that pregnant women should receive unadjuvanted vaccine where possible, but that an adjuvanted vaccine could be used if necessary.

Kieny also said the WHO is discussing with manufacturers how to provide enough free or reduced-price vaccine to cover healthcare workers in all developing countries. She noted that donations of 100 million and 50 million doses have been pledged so far.
(CIDRAP 8/6/09)

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Global: Two health care workers die of pandemic influenza 2009 H1N1 infection
A 51-year-old California nurse who worked on a cancer unit at a hospital in Carmichael died of a novel H1N1 flu infection, according to reports on 31 Jul 2009. A hospital spokesman said authorities don't know if she was exposed to the virus at the hospital or elsewhere. Her death certificate said she also had pneumonia and was infected with methicillin-resistant Staphylococcus aureus. Meanwhile, a pediatric nurse in New Zealand recently died of a novel H1N1 infection, local media reported. Health care workers are often identified as a priority group for the pandemic H1N1 vaccine.
(CIDRAP 7/31/09)

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Asia
Australia (New South Wales): Pandemic influenza 2009 H1N1 confirmed in swine
Tests have confirmed that pandemic influenza H1N1 has broken out at a piggery in the central west of New South Wales (NSW). It is the first case of the virus among pigs in Australia and the State Government believes the animals probably caught the disease from workers at the piggery. A total of 280 pigs have been placed in quarantine and strict biosecurity measures are in place to try to contain the spread of the virus. NSW Primary Industries Minister Ian Macdonald says the piggery's owner and staff have previously suffered flu-like symptoms and are being tested for pandemic influenza H1N1. Macdonald says the outbreak poses no threat to humans.
(ProMED 8/1/09)

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Chinese Taipei, Hong Kong: Influenza H3N2 circulating with pandemic H1N1 2009 virus
Chinese Taipei announced two more cases of influenza virus on 31 Jul 2009. One is down with the influenza pandemic (H1N1) 2009 virus, and the other is infected with influenza A virus subtype H3N2. As of 31 Jul 2009, Taiwan had six cases of H1N1 and two H3N2 cases. The Taipei Center for Disease Control said that Taipei is faced with threats of two flu types. The center said among the six H1N1 cases, one has died. In addition, the center said that in the month of July 2009 alone, there had been 10 cases of H1N1 cluster infections. There are at least 58 confirmed cases of pandemic H1N1.

The deputy director-general of the center, Lin Ting, said that since most of the infected are men in their 30s, these men are being considered for receiving the vaccines as well. Head of the physical education department of the education ministry Wang Jun-chuan said on 31 Jul 2009 that schools have the right to decide whether to stop classes if cases were to appear in schools.

"We have been in touch with the Taipei Centers of Disease Control. If a school were to have one infected case, we have agreed that the school can discuss with the county government and the health department about whether to stop classes for up to seven days. But if the situation is serious, this can extended to 10 days. Secondly, if the county happens to have more than two cases in a school or a case of cluster infection, then the health department can decide for all schools in the district or nearby region to be shut down," said Wang.

Meanwhile, Hong Kong's health authorities announced 27 Jul 2009 that a new variant of the H3N2 seasonal influenza virus has been found. The Brisbane strain has been the prevalent circulator of H3N2 in the past year, and the new variant is its direct descendent, said Thomas Tsang, controller of Hong Kong's Center for Health Protection (CHP). "However, it has some genetic changes distinguishing it from the old Brisbane strain," he said. He said it is normal for viruses to go through changes, adding that overseas health authorities, including those in Canada, Britain and Australia, had also found the new variant.

Tsang said although vaccines provided for the northern hemisphere may not be a direct match for this new variant, they will still provide some protection. According to the CHP, H3N2 accounts for 43 percent of flu viruses circulating in Hong Kong, while A/H1N1 accounts for 49 percent. Officials from the two economies will meet to discuss response to the pandemic influenza H1N1 2009 in August 2009.
(ProMED 8/2/09)

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Indonesia: Girl hospitalized with suspected avian influenza H5N1
A 17-year-old girl was admitted 31 Jul 2009 to the Wahidin Sudirohusodo Hospital in South Sulawesi, with what is suspected to be an H5N1 infection. Hospital spokesman, Khalid Saleh, said the teenager displayed symptoms of avian flu, including fever, cough, nausea, and suffocation. She became sick after a number of chickens around her home suddenly died. A doctor who treated her said her temperature exceeded 39C for three days and that she displayed other symptoms of avian flu, Khalid said. The teenager is now receiving treatment in an isolation room, under the close watch of medical workers. A government team had been assigned to conduct surveillance in the girl's neighborhood in the Sudiang subdistrict in an effort to prevent the spread of the virus.
(ProMED 7/31/09)

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Russia: Official warns against travel to the UK due to pandemic influenza 2009 H1N1 outbreaks
Russia's chief health officer, Gennadi Onischenko, urged Russians not to travel to Wales for a World Cup soccer match on 9 Sep 2009 because of Britain's novel H1N1 flu epidemic, according to the British newspaper the Times. Onischenko blamed Britain for most of Russia's pandemic H1N1 cases and called travel there "absolutely inappropriate." The story said Wales is the least affected part of the country, with 89 confirmed cases and no deaths.
(CIDRAP 8/4/09)

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Americas
Argentina: Pace of pandemic influenza 2009 H1N1 has slowed
Argentina's pandemic H1N1 cases have peaked, and so far the death rate from the disease seems to be less than for seasonal flu, said public health experts on 31 Jul 2009. However, one official said the disease has had its greatest impact on young people. Scientists report that viruses isolated in Argentina are nearly identical to those circulating in North America.
(CIDRAP 8/3/09)

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North America: PAHO rejects report of resistant pandemic H1N1 cases on US-Mexico border
A Pan American Health Organization (PAHO) official on 4 Aug 2009 rejected a media report that quoted her as saying that antiviral-resistant cases of novel H1N1 influenza had been found along the US-Mexican border. Details in the original article, published by Agence France-Presse (AFP), were sketchy and at times confusing. The report, which quoted Maria Teresa Cerqueira, PhD, chief of PAHO's US-Mexico border office in El Paso, Texas, said a few oseltamivir (Tamiflu)-resistant cases had been detected in El Paso and near McAllen, Texas. The story quoted her as saying one patient diagnosed with a resistant strain had been treated with zanamivir (Relenza) and that "another was given no alternative treatment." The article didn't say if either of the patients was initially treated with Tamiflu.

But in an e-mail message, Cerqueira said she was misquoted. She sent the message to PAHO. Cerqueria wrote that she mentioned McAllen and El Paso as being among the border towns where novel flu virus has been detected. She said that in response to a question about resistant cases, she said she was concerned and that PAHO has recommended surveillance for such cases, especially since people go back and forth across the border for medical care and to buy medicine. Cerqueira said she repeated that she had no information on any antiviral-resistant cases in the border area. "It is an unfortunate misinterpretation that needs to be clarified," she wrote.

So far, oseltamivir-resistant novel flu cases have been confirmed in Denmark, Hong Kong, Japan, and Canada. All of the patients had a history of oseltamivir prophylaxis or treatment, except for the patient in Hong Kong, a girl who was visiting from the US, where officials believe she was exposed to the virus.
(CIDRAP 8/4/09)

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USA: Some experts call for more use of pneumococcal vaccine in pandemic influenza H1N1 battle
Some infectious disease experts say the pneumococcal vaccine Pneumovax should be used more widely as a way to prevent serious cases of novel H1N1 flu, the Los Angeles Times reported on 4 Aug 2009. Preliminary CDC data indicate that about 30% of H1N1-related pneumonia cases are caused by Streptococcus pneumoniae, which is targeted by Pneumovax. At least 70 million Americans are in groups advised to receive the vaccine, but coverage among non-elderly groups is fairly low.
(CIDRAP 8/4/09)

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2. Infectious Disease News

Asia
China (Qinghai): Outbreak of pneumonic plague kills three, thousands quarantined
A dog is suspected to be the origin of an outbreak of pneumonic plague in northwest China that has killed three people and left 10,000 under strict quarantine. Ziketan, a remote town in a Tibetan area of Qinghai province, has been locked down since 1 Aug 2009 in an effort to contain the spread of the highly virulent disease. One patient was in critical condition and eight others were infected, most of them relatives of the first fatality, a 32-year-old herdsman, or local doctors, Xinhua news agency said.

Initial tests had shown that the herdsman's dead dog was the likely origin of the outbreak, stated professor Wang Hu, director of the Qinghai disease control bureau. Wang said it was likely that the dog died after eating a plague-infected marmot and that the man became infected when he was bitten by fleas while burying the dead dog. He died three days later."The first victim buried the dead dog without any protection. After he became infected, his relatives and neighbors were in close contact with him without taking any protective measures, leading to their infection," Wang said. At present, 218 people are quarantined in hospital, and 115 of them had been in close contact with those infected.
(ProMED 8/6/09)

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Russia (Chelyabinsk): Update of tick-borne encephalitis in 2009
Since the beginning of 2009, a total of 316 people, including 52 children, have been hospitalized in the Chelyabbinsk Oblast for suspected tick-borne encephalitis (TBE) virus infection. Diagnosis of TBE virus infection has been confirmed in 19 adult cases and in one child. None were vaccinated and none received emergency treatment with immunoglobulin. There has been one fatality, a 49-year-old from Zlatoust. A total of 15,126 people sought treatment at health care facilities as a result of tick bites in 2009, including 700 during the last week of July 2009.

The health care services of the Chelyabinsk Oblast are responsible for implementing an immunization program against TBE virus infection. Through August 2009, 165,000 people, including 101,636 children, have been immunized. Treatments against tick infestation have been applied over an area of 4000 hectares, including 598.8 hectares of recreational land. During July 2009 outdoor activities for children, such as hiking and excursions, have been restricted to these treated areas.
(ProMED 7/31/09)

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Singapore: 3 clusters of malaria under investigation, suspected local transmission
The Ministry of Health (MOH) is currently investigating three clusters of suspected local malaria transmission involving a total of 14 people. As of 6 Jun 2009, all but two cases had been discharged. All 14 cases had no recent travel history overseas, suggesting that there is possible local transmission.

The first cluster involves five cases comprising male foreign workers aged between 25 to 37 years at Jurong Island. The cases had onset of illness 3 to 25 May 2009 with symptoms such as fever, headache and chills. Four of the cases stayed at a dormitory on Jurong Island and work at the same site on Jurong Island. The fifth case works on Jurong Island close to the dormitory and worksite of the other four cases. The second cluster involves nine cases aged between 20 and 40 years in the Sungei Kadut/Mandai area comprised of eight foreign workers and one full-time national serviceman. The cases had onset of illness between 16 and 30 May 2009 with symptoms such as fever, headache and chills.

The third cluster consists of four cases near a row of shop houses located at the junction of Sembawang Road and Admiralty Road East. The first case is a 24-year-old Singaporean woman who works in the area. Her illness started on 30 Jun 2009 and she was admitted to hospital on 20 Jul 2009. She does not have any recent travel history or past history of malaria.

The second and third cases involve colleagues -- a 49-year-old Singaporean man and a 40-year-old Singaporean woman. They frequented a coffee shop at the row of shop houses. The male patient fell sick on 11 Jul 2009 and was admitted to hospital four days later. His colleague fell ill on 12 Jul 2009 and was hospitalized on 17 Jul 2009. The fourth case is a 24-year-old male foreign worker who was picked up during MOH's active case finding in the vicinity. He stayed at a nursery beside the row of shop houses and first had symptoms on 12 Jun 2009. He was admitted to hospital on 28 Jul 2009.

The third cluster is not related to the previous two clusters as none of the four cases had visited Jurong Island or Mandai/Sungei Kadut prior to their illness.
(ProMED 7/30/09)

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Americas
USA: Salmonellosis outbreak prompts ground beef recall
Beef Packers, Inc., a Fresno, California, establishment, is recalling approximately 825,769 pounds (375 tons) of ground beef products that may be linked to an outbreak of salmonellosis, the US Department of Agriculture's Food Safety and Inspection Service (FSIS) announced 6 Aug 2009. Details on the recall are available at http://www.fsis.usda.gov/News_&_Events/Recall_041_2009_Release/index.asp. This particular strain of S. Newport is resistant to many commonly prescribed drugs, which can increase the risk of hospitalization or possible treatment failure in infected individuals.
(ProMED 8/6/09)

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USA (Minnesota): Cases of serious tick-borne disease in 2008 and 2009
Two serious tick-borne diseases have surfaced in Minnesota, and one claimed the life of a child in Dakota County, officials said 29 Jul 2009. The diseases, Rocky Mountain spotted fever and Powassan encephalitis, are rare in Minnesota but pose grave risks to patients who contract them. The child died due to Rocky Mountain spotted fever.

This type of encephalitis, also known as Powassa (POW) disease, struck a child in Cass County in 2008 and an adult in the same county in 2009. Both patients were hospitalized with severe neurological symptoms and require ongoing care, according to the department. Since this encephalitis virus was first identified in 1958 in Powassan, Ontario, about 50 cases have been reported in the US and Canada. The patients in Minnesota represent the western-most human cases identified in North America, state health officials said. Signs and symptoms of Powassa disease appear within two weeks of an infectious tick bite. Many patients never see the tick that bit them. People with POW encephalitis or meningitis may have fever, headache, vomiting, weakness, confusion, loss of coordination, speech difficulties, and memory loss. Long-term problems are common, and about 10 percent of reported cases result in death.
(ProMED 7/30/09)

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USA (Utah): Rabid bats attack girls in Weber County
Two young girls visiting northern Utah have begun treatment for rabies after being attacked in broad daylight by a bat that later tested positive for the disease. The Weber-Morgan Health Department reported the attack took place on 1 Aug 2009 as the girls were walking near the town of Liberty. One was bitten on the finger and the other was exposed to the disease while trying to stop the attack. Officials said relatives were able to safely capture the bat, which tested positive for rabies. The girls are receiving a series of shots to prevent them from contracting the disease.
(ProMED 8/5/09)

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3. Updates
INFLUENZA A/H1N1
The following websites provide the most current information, surveillance, and guidance.

- 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
(WHO; US CDC; MOH Mexico; PHAC; PAHO; CIDRAP; ProMED)

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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
Viet Nam
The central Department of Preventive Medicine and Environment has asked provincial health departments and preventive medicine centers nationwide to spray chemicals at least twice a year to kill mosquito larvae to prevent dengue fever. Nguyen Thuy Hoa of the Central Epidemic Hygiene Institute said there would be a pilot project to spray chemicals in lakes and ponds to prevent the development of mosquito larvae. However, lakes and ponds may be breeding sites for various mosquitoes, but not for Aedes aegypti or Ae. albopictus, the dengue virus vectors. The institute had been carrying out research to use Wolbachia, a bacterium that infects arthropods to shorten the life spans of mosquitoes, he said. Nam said Viet Nam has successfully bred and multiplied Wolbachia and the department would choose some areas where mosquito populations live to release the bacteria.

According to a department report, 36,046 dengue cases were reported nation-wide up to 19 Jul 2009, a 11.7 percent increase over the same period in 2008. Cases were mostly in the southern region. Nam explained that since most water in the southern region is brackish, residents use containers to store water, which act as reservoirs for mosquitoes.
(ProMED 8/3/09)

Mexico
Authorities of the Secretariat of Health of Hidalgo state, detected an outbreak of at least 100 cases of classical dengue in the municipality of San Felipe Orizatlan. The report resulted in the mobilization of medical brigades to the area who are also collaborating on joint projects with the authorities of San Luis Potosi, the locale neighboring this region. The cumulative total of dengue cases in the Huasteca zone of Hidalgo during the first half of 2009 is 203 cases. The year 2008 ended with 609 cases. The municipalities of Huejutla and Atlapexco have also been affected by dengue.
(ProMED 8/3/09)

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4. Articles
Public Health and Medical Responses to the 1957-58 Influenza Pandemic
Henderson DA et al. Biosecurity & Bioterrorism: Biodefense Strategy, Practice, and Science. 2009; 7(3). Available at http://www.liebertonline.com/doi/pdfplus/10.1089/bsp.2009.0729?cookieSet=1.

As the U.S. prepares to respond this fall and winter to pandemic (H1N1) 2009, a review of the 1957-58 pandemic of Asian influenza (H2N2) could be useful for planning purposes because of the many similarities between the 2 pandemics. Using historical surveillance reports, published literature, and media coverage, this article provides an overview of the epidemiology of and response to the 1957-58 influenza pandemic in the U.S., during which an estimated 25% of the population became infected with the new pandemic virus strain. While it cannot be predicted with absolute certainty how the H1N1 pandemic might play out in the U.S. this fall, lessons from the 1957-58 influenza pandemic provide useful and practical insights for current planning and response efforts.

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Evaluation of Rapid Influenza Diagnostic Tests for Detection of Novel Influenza A (H1N1) Virus--United States, 2009
US Centers for Disease Control and Prevention. MMWR. 7 Aug 2009; 58(30): 826-829. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5830a2.htm.

The recent appearance and worldwide spread of novel influenza A (H1N1) virus has highlighted the need to evaluate commercially available, widely used, rapid influenza diagnostic tests (RIDTs) for their ability to detect these viral antigens in respiratory clinical specimens. As an initial assessment, CDC conducted an evaluation of multiple RIDTs. Sixty-five clinical respiratory specimens collected during April--May 2009* that had previously tested positive either for novel influenza A (H1N1) or for seasonal influenza A (H1N1) or A (H3N2) viruses by real-time reverse transcription--polymerase chain reaction (rRT-PCR) assay were used in the evaluation. The results showed that, although the RIDTs were capable of detecting novel A (H1N1) virus from respiratory specimens containing high levels of virus (as indicated by low cycle threshold [Ct] values), the overall sensitivity was low (40%--69%) among all specimens tested and declined substantially as virus levels decreased (and Ct values increased). These findings indicate that, although a positive RIDT result can be used in making treatment decisions, a negative result does not rule out infection with novel influenza A (H1N1) virus. Patients with illnesses compatible with novel influenza A (H1N1) virus infection but with negative RIDT results should be treated empirically based on the level of clinical suspicion, underlying medical conditions, severity of illness, and risk for complications. If a more definitive determination of infection with influenza virus is required, testing with rRT-PCR or virus isolation should be performed. Additional evaluations of the accuracy of RIDTs in detecting novel influenza A (H1N1) virus should be conducted. (Excerpt with references removed.)

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Facemasks and Hand Hygiene to Prevent Influenza Transmission in Households
Cowling BJ et al. Ann Intern Med. 6 Oct 2009; 151(7). Available at http://www.annals.org/cgi/content/full/0000605-200910060-00142v1.

Background: Few data are available about the effectiveness of nonpharmaceutical interventions, such as hand hygiene and facemasks, for preventing influenza virus transmission.

Objective: To investigate whether hand hygiene and use of facemasks prevents household transmission of influenza.

Design: Cluster randomized controlled trial. Randomization was computer generated; allocation was concealed from treating physicians and clinics and implemented by study nurses at the time of the initial household visit. Participants and personnel administering the interventions were not blinded to group assignment.

Setting: Households in Hong Kong. Patients: 407 people presenting to outpatient clinics with influenza-like illness who were positive for influenza A or B virus by rapid testing (index patients) and 794 household members (contacts) in 259 households.

Intervention: Lifestyle education (control) (134 households), hand hygiene (136 households), or surgical facemasks plus hand hygiene (137 households) for all household members.

Measurements: Influenza virus infection in household contacts, as confirmed by reverse transcription polymerase chain reaction (RT-PCR) or diagnosed clinically after 7 days.

Results: Sixty (8%) household contacts in the 259 households had RT-PCR–confirmed influenza virus infection in the 7 days after intervention. Hand hygiene without or with facemasks seemed to reduce influenza transmission, but the differences in transmission compared with the control group were not statistically significant. In 154 households in which interventions were implemented within 36 hours of symptom onset in the index patient, transmission of RT-PCR–confirmed infection seemed to be reduced, an effect attributable to reductions in infection among participants using facemasks plus hand hygiene (adjusted odds ratio, 0.33 [95% CI, 0.13 to 0.87]). Adherence to interventions was variable. Limitation: The delay from index patient symptom onset to intervention and variable adherence may have mitigated intervention effectiveness.

Conclusion: Hand hygiene and facemasks seemed to prevent household transmission of influenza virus when implemented within 36 hours of index patient symptom onset. These findings suggest that nonpharmaceutical interventions are important for mitigation of pandemic and interpandemic influenza.

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Safety and Efficacy of Extended-Duration Antiviral Chemoprophylaxis Against Pandemic and Seasonal Influenza
Khazeni N et al. Ann Intern Med. 6 Oct 2009; 151(7). Available at http://www.annals.org/cgi/content/full/0000605-200910060-00143v1.

Background: Neuraminidase inhibitors (NAIs) are stockpiled internationally for extended use in an influenza pandemic.

Purpose: To evaluate the safety and efficacy of extended-duration (>4 weeks) NAI chemoprophylaxis against influenza.

Data Sources: Studies published in any language through 11 June 2009 identified by searching 10 electronic databases and 3 trial registries. Study Selection: Randomized, placebo-controlled, double-blinded human trials of extended-duration NAI chemoprophylaxis that reported outcomes of laboratory-confirmed influenza or adverse events.

Data Extraction: 2 reviewers independently assessed study quality and abstracted information from eligible studies.

Data Synthesis: Of 1876 potentially relevant citations, 7 trials involving 7021 unique participants met inclusion criteria. Data were pooled by using random-effects models. NAI chemoprophylaxis decreased the frequency of symptomatic influenza (relative risk [RR], 0.26 [95% CI, 0.18 to 0.37]; risk difference [RD], –3.9 percentage points [CI, –5.8 to –1.9 percentage points]) but not asymptomatic influenza (RR, 1.03 [CI, 0.81 to 1.30]; RD, –0.4 percentage point [CI, –1.6 to 0.9 percentage point). Adverse effects were not increased overall among NAI recipients (RR, 1.01 [CI, 0.94 to 1.08]; RD, 0.1 percentage point [CI, –0.2 to 0.4 percentage point), but nausea and vomiting were more common among those who took oseltamivir (RR, 1.48 [CI, 1.86 to 2.33]; RD, 1.7 percentage points [CI, 0.6 to 2.9 percentage points]). Prevention of influenza did not statistically significantly differ between zanamivir and oseltamivir.

Limitations: All trials were industry-sponsored. No study was powered to detect rare adverse events, and none included diverse racial groups, children, immunocompromised patients, or individuals who received live attenuated influenza virus vaccine.

Conclusion: Extended-duration zanamivir and oseltamivir chemoprophylaxis appears to be highly efficacious for preventing symptomatic influenza among immunocompetent white and Japanese adults. Extended-duration oseltamivir is associated with increased nausea and vomiting. Safety and efficacy in several subpopulations that might receive extended-duration influenza chemoprophylaxis are unknown.

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Supply and safety issues surrounding an H1N1 vaccine
Lancet editorial. 1 Aug 2009; 374(9687): 358. Available at http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61395-7/fulltext.

Editorial
Last week, Australia and the USA announced that they would begin trials of an H1N1 vaccine. Vaccination against H1N1 will be an important development in controlling the impact of the pandemic. However, several thorny issues exist around vaccine manufacture and approval. All countries will require the vaccine but current global manufacturing capacity will not be able to meet this demand. Additionally, experts think that individuals might need two doses of the vaccine. . . (Excerpt.)

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Zanamivir-Resistant Influenza Viruses with a Novel Neuraminidase Mutation
Hurt AC et al. Journal of Virology. 29 Jul 2009. Early online publication. Available at http://www.ncbi.nlm.nih.gov/pubmed/19641000?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum.

The neuraminidase inhibitors zanamivir and oseltamivir are marketed for the treatment and prophylaxis of influenza, and have been stockpiled by many countries for use in a pandemic. Although recent surveillance has identified a striking increase in the frequency of oseltamivir resistant seasonal A(H1N1) viruses in Europe, USA, Oceania and South Africa, to date there have been no reports of significant zanamivir resistance among A(H1N1) viruses or any other human influenza viruses. We investigated the frequency of oseltamivir and zanamivir resistance in circulating seasonal A(H1N1) influenza viruses in Australasia and South East Asia. Analysis of 391 A(H1N1) influenza viruses isolated between 2006 and early 2008 from Australasia and South East Asia revealed nine viruses (2.3%) which demonstrated markedly reduced zanamivir susceptibility and contained a previously undescribed Gln136Lys (Q136K) neuraminidase mutation. The mutation had no effect on oseltamivir susceptibility, but caused approximately a 300-fold and a 70-fold reduction in zanamivir and peramivir susceptibility, respectively. The role of the Q136K mutation in conferring zanamivir resistance was confirmed using reverse genetics. Interestingly, the mutation was not detected in the primary clinical specimens from which these mutant isolates were grown, suggesting that the resistant viruses either occurred in very low proportions in the primary clinical specimens or arose during MDCK cell culture passage. Compared to susceptible A(H1N1) viruses, the Q136K mutant strains displayed greater viral fitness than the wildtype virus in MDCK cells, but equivalent infectivity and transmissibility in a ferret model.

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Artemisinin Resistance in Plasmodium falciparum Malaria
Dondorp AM et al. NEJM. 30 Jul 2009; 361(5): 455-467. Available at http://content.nejm.org/cgi/content/full/361/5/455.

ABSTRACT
Background Artemisinin-based combination therapies are the recommended first-line treatments of falciparum malaria in all countries with endemic disease. There are recent concerns that the efficacy of such therapies has declined on the Thai–Cambodian border, historically a site of emerging antimalarial-drug resistance.

Methods In two open-label, randomized trials, we compared the efficacies of two treatments for uncomplicated falciparum malaria in Pailin, western Cambodia, and Wang Pha, northwestern Thailand: oral artesunate given at a dose of 2 mg per kilogram of body weight per day, for 7 days, and artesunate given at a dose of 4 mg per kilogram per day, for 3 days, followed by mefloquine at two doses totaling 25 mg per kilogram. We assessed in vitro and in vivo Plasmodium falciparum susceptibility, artesunate pharmacokinetics, and molecular markers of resistance.

Results We studied 40 patients in each of the two locations. The overall median parasite clearance times were 84 hours (interquartile range, 60 to 96) in Pailin and 48 hours (interquartile range, 36 to 66) in Wang Pha (P<0.001). Recrudescence confirmed by means of polymerase-chain-reaction assay occurred in 6 of 20 patients (30%) receiving artesunate monotherapy and 1 of 20 (5%) receiving artesunate–mefloquine therapy in Pailin, as compared with 2 of 20 (10%) and 1 of 20 (5%), respectively, in Wang Pha (P=0.31). These markedly different parasitologic responses were not explained by differences in age, artesunate or dihydroartemisinin pharmacokinetics, results of isotopic in vitro sensitivity tests, or putative molecular correlates of P. falciparum drug resistance (mutations or amplifications of the gene encoding a multidrug resistance protein [PfMDR1] or mutations in the gene encoding sarco–endoplasmic reticulum calcium ATPase6 [PfSERCA]). Adverse events were mild and did not differ significantly between the two treatment groups.

Conclusions P. falciparum has reduced in vivo susceptibility to artesunate in western Cambodia as compared with northwestern Thailand. Resistance is characterized by slow parasite clearance in vivo without corresponding reductions on conventional in vitro susceptibility testing. Containment measures are urgently needed.

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Laboratory-Acquired Vaccinia Virus Infection--Virginia, 2008
US Centers for Disease Control and Preventation. MMWR. 31 July 2009; 58(29): 797-800. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5829a1.htm?s_cid=mm5829a1_e.

Vaccinia virus (VACV) is the live viral component of smallpox vaccine. Inadvertent exposure to VACV can result in infection, and severe complications can occur in persons with underlying risk factors (e.g., pregnancy, immunodeficiencies, or dermatologic conditions). The Advisory Committee on Immunization Practices (ACIP) recommends smallpox vaccination for laboratory workers who handle nonhighly attenuated VACV strains or other orthopoxviruses (e.g., monkeypox, cowpox, or variola). On July 8, 2008, CDC was notified by a Virginia physician of a suspected case of inadvertent autoinoculation and VACV infection in an unvaccinated laboratory worker. This report describes the subsequent investigations conducted by the Virginia Department of Health and CDC to identify the source of infection and any cases of contact transmission. Of the patient's 102 possible contacts, seven had underlying risk factors for developing serious vaccinia infection. Investigators found no evidence of contact transmission and, based on the results of molecular typing, further concluded that the patient had been exposed to a VACV strain that had contaminated the seed stock from the laboratory where the patient worked. This case underscores the importance of adherence to ACIP vaccination recommendations for laboratory workers and use of safety precautions when working with nonhighly attenuated VACV. (Excerpt with references removed.)

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5. Notifications
US Centers for Disease Control and Prevention tools and resources updated
Novel H1N1 Vaccination Recommendations: http://www.cdc.gov/h1n1flu/vaccination/acip.htm
Managing Calls and Call Centers during a Large-Scale Influenza Outbreak: Implementation Tool: http://www.cdc.gov/h1n1flu/callcenters.htm
Preparing for Vaccination with Novel H1N1 Vaccine: http://www.cdc.gov/h1n1flu/vaccination/provider/preparing.htm
School Dismissal Monitoring System: http://www.cdc.gov/h1n1flu/schools/dismissal_form/index.htm/?scan.

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Weekly Epidemiological Record Bulletin
WHO. 31 July 2009; 84(31): 309-324. Available at http://www.who.int/wer.

Contents include:
Cholera: global surveillance summary, 2008
WHO cholera information sources on the web

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International Swine Flu Conference
Dates: 19-20 August 2009; Location: Washington, DC

Learning objectives for the conference:
- Maintaining cash flow and work flow--keeping the business process alive.
- How to plan--making everyone a stakeholder and spelling out roles and responsibilities.
- Protecting your community--knowing your resources and testing them against your toughest scenarios.

Additional information available at http://new-fields.us/em/link.php?M=9950864&N=90&L=187&F=T.

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 apecein@u.washington.edu