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EINet Alert ~ Apr 24, 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
- Cumulative number of human cases of avian influenza A/(H5N1)
- China (Tibet): Confirmed new outbreak of avian influenza H5N1 in poultry in Lhasa
- Canada: Adjusting national antiviral stockpile due to concern over ostelamivir resistance
- Mexico: Canadian officials to assist in probe for cause of severe respiratory illnesses in Mexico
- USA (California, Texas): CDC confirms 7 human cases of unusual swine influenza
- USA: Swine influenza cases recall 1976 episode
- Egypt: Four new human cases of avian influenza H5N1, two deaths

2. Updates
- AVIAN/PANDEMIC INFLUENZA

3. Articles
- Avian influenza at both ends of a migratory flyway: characterizing viral genomic diversity to optimize surveillance plans for North America
- Comparison of the trivalent live attenuated vs. inactivated influenza vaccines among U.S. military service members
- Swine Influenza A (H1N1) Infection in Two Children--Southern California, March--April 2009

4. Notifications
- Influenza in the Asia-Pacific
- Conference: ICU Infection in an Era of Multi-Resistance


1. Influenza News

Global
Cumulative number of human cases of avian influenza A/(H5N1)
Economy / Cases (Deaths)

2009
China/ 7 (4)
Egypt/ 16 (0)
Viet Nam/ 3 (3)
Total/ 26 (7)

***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: 421 (257).
(WHO 4/23/09 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 3/23/09)

WHO's maps showing world's areas affected by H5N1 avian influenza (last updated 4/15/09): http://gamapserver.who.int/mapLibrary/

WHO’s timeline of important H5N1-related events (last updated 3/23/09):
http://www.who.int/csr/disease/avian_influenza/ai_timeline/en/index.html

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Asia
China (Tibet): Confirmed new outbreak of avian influenza H5N1 in poultry in Lhasa
China's Ministry of Agriculture (MOA) confirmed on19 Apr 2009, a new outbreak of bird flu in Lhasa, southwestern Tibet Autonomous Region. The national bird flu laboratory confirmed that the H5N1 bird flu virus was found in poultry sold at a poultry wholesale market in Chengguan District of Lhasa on 12 Apr 2009.

Emergency measures have been taken and the epidemic has been brought under control, the MOA said and 1679 fowl were culled after the outbreak. According to the local health department, no abnormalities were found among people in contact with the poultry, the ministry said.
(ProMED 4/19/09)

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Americas
Canada: Adjusting national antiviral stockpile due to concern over ostelamivir resistance
Canada will adjust the combination of antiviral medications in its national emergency stockpile because of concern about ostelamivir (Tamiflu) resistance among influenza viruses, the Canadian Press (CP) reported on 20 Apr 2009. The Public Health Agency of Canada said it will boost its supply of zanamivir (Relenza), along with older antiviral medications such as amantadine and rimantadine. Canada's emergency stockpile, a backup to the country's national antiviral stockpile, currently contains 14 million doses, enough to treat 1.4 million people. Arlene King, a federal pandemic planning official, stated that discussions are under way with provincial and local officials to also adjust the mix of medications in the national antiviral stockpile, which holds most of the country's pandemic flu drugs—55.7 million doses, enough to treat about 5.6 million people.
(CIDRAP 4/20/09)

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Mexico: Canadian officials to assist in probe for cause of severe respiratory illnesses in Mexico
Canada's Public Health Authority (PHAC) said 23 April 2009 in a situation update that Mexican authorities have asked its assistance in determining the cause of two clusters of severe respiratory illnesses that have occurred in April 2009.

The illness has killed at least 60 people and sickened nearly 1,000, health officials said on 24 April 2009. Fifty-seven people have died in Mexico City, the World Health Organization said on 24 April 2009. Three deaths were reported from other locations: one from Oaxaca in southern Mexico and two from Baja California Norte, near the US border.

As a precaution to avoid further contamination, schools and universities in Mexico City and the state of Mexico were closed on 24 April 2009, said the national health secretary, Jose Angel Cordova Villalobos. He said the schools may remain closed for a while.

Sixteen of the deaths were from "a new type of influenza virus," Cordova said. Another 45 cases are "suspicious," he said. Authorities are investigating the cases of 943 people suffering from a viral infection, the health minister said. The World Health Organization had said 800 people had fallen ill.

The PHAC report said the disease outbreak struck some healthcare workers and that most patients were previously healthy young adults between the ages of 25 and 44. Symptoms included fever, headache, ocular pain, shortness of breath, and fatigue that rapidly progressed to severe respiratory distress in about five days.

Mexican officials detected some influenza A/H1N1 and influenza B viruses, but have apparently ruled out H5N1 virus involvement. The PHAC said it received 51 clinical samples from Mexico for testing at its National Microbiology Lab.

Mexico told the PHAC that it had a late influenza season with an increasing number of influenza-like illnesses since the middle of March. The country also had a higher proportion of influenza B viruses than previous seasons.

There is concern that the outbreak in Mexico is connected to the cases of swine influenza in California and Texas in the United States. However, at this point there have been no cases confirmed to be swine influenza in Mexico.
(CNN 4/24/09, Veratect 4/24/09, CIDRAP 4/23/09)

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USA (California, Texas): CDC confirms 7 human cases of unusual swine influenza
Seven cases of an unusual swine influenza virus infection have surfaced in the United States (US) raising concern about possible human-to-human transmission and putting health authorities on alert, officials from the US Centers for Disease Control and Prevention (CDC) announced. Two cases were announced on 21 April 2009 and are children in Southern California. The remaining five cases were announced on 23 April 2009 and include two clusters: two 16-year-old boys in San Antonio, Tex., who attended the same school and a father and daughter from San Diego County. The fifth case occurred in a patient from Imperial County, which borders San Diego County.

Anne Schuchat, MD, interim deputy director for the CDC's science and public health program, told reporters that the clusters are consistent with human-to-human spread. But she also said that the World Health Organization (WHO) has not raised its six-phase pandemic alert level above phase three (no or very limited human-to-human transmission).

The first two cases were a 10-year-old boy in San Diego County and a 9-year-old girl in neighboring Imperial County, but they are apparently unrelated, the CDC said on 21 April 2009. Details of these two infections were detailed in the CDC’s Morbidity and Mortality Weekly Report on 21 April 2009. Full text is available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm58d0421a1.htm.

Novel strain, relatively mild symptoms
Concerning the seven American cases, Schuchat said, "The good news is that all of the patients have recovered, and one was hospitalized. This is not looking like a very severe influenza." Patients experienced fever, cough, and sore throat symptoms similar to typical influenza, but some of the patients who had swine influenza also experienced more diarrhea and vomiting than is typical of seasonal flu.

The CDC said genetic sequencing of samples from the first two patients show that the swine flu virus contains segments from four different viruses: some North American swine, some North American avian, one human influenza, and two Eurasian swine. "This virus hasn't been recognized in the USA or elsewhere," Schuchat said.

CDC scientists have determined that the novel swine flu virus is resistant to the older antivirals rimantadine and amantadine but is susceptible to oseltamivir and zanamivir. Schuchat said the CDC expects to see more swine flu cases and that it would provide regular updates on its Website. "This is not time for major concern around the country, but we want you to know what's going on," she said. Most of the public health response will focus on the California and Texas areas where cases have been identified, but the CDC is urging health departments in other states to heighten their awareness of respiratory illnesses, particularly in those who have had contact with pigs or traveled to the San Diego or San Antonio areas.

Schuchat said the CDC doesn't know yet if the H1N1 component of this season's influenza vaccine provides any protection against the swine flu virus, but she said studies are under way to determine if there is any cross-protection.

The CDC said it received reports of 12 human swine flu cases from December 2005 through January 2009, an increase from the previous long-term average of about one case every 1 to 2 years. The "vast majority" of such cases do not lead to human-to-human transmission, but all need to be investigated thoroughly, the agency stated.
(CIDRAP 4/23/09, CIDRAP 4/21/09)

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USA: Swine influenza cases recall 1976 episode
Swine influenza viruses have never been documented as the cause of a human influenza pandemic, but in 1976 they generated pandemic fears strong enough to trigger a nationwide vaccination campaign. The reporting of swine flu cases in two California children on 21 April 2009 stirred memories of the 1976 episode, which caused embarrassment for public health authorities when the pandemic never materialized.

The Centers for Disease Control and Prevention (CDC) announced on 21 April 2009 that two children in southern California fell ill in late March with what turned out to be swine flu infections. Both of the children recovered, and neither was hospitalized.

But the cases raised concern because neither child had any known exposure to pigs, suggesting that human-to-human transmission might have occurred. Further, the virus was found to be a new strain of swine influenza A/H1N1 that differs substantially from human H1N1 strains. That suggested that much of the population could be susceptible to it and that the H1N1 antigen in seasonal flu vaccines probably would not protect people, the CDC said.

Officials are testing contacts of the two children, including four family members who also were recently sick, to see if they have antibodies indicating they were infected with the H1N1 virus. CDC spokesman Tom Skinner said it would be several days or possibly weeks before the results are available.

Human swine flu infections are rare but have become slightly more frequent in recent years, with 14 cases (including the two in California) since December 2005, according to the CDC. Almost always the infection has been associated with exposure to pigs, which are very commonly infected. Ken August, a spokesman for the California Department of Public Health, said on 22 April 2009 that until the two latest cases, no human cases of swine flu had been identified in California in several years.

Very rarely have people with swine flu infections been known to pass the infection to someone else. One such case occurred in Wisconsin in 1988, when a pregnant woman fell ill after visiting a swine exhibition, according to the CDC. She was hospitalized with pneumonia and died eight days later. Follow-up studies suggested that "one to three" healthcare workers who had contact with her had mild flu-like illnesses and antibody evidence of swine flu infection.

Far better known is the swine flu episode of 1976. About 200 soldiers in basic training at Fort Dix in New Jersey fell ill in January and February 1976, according to a 2006 article by Richard Krause, who was director of the National Institute of Allergy and Infectious Diseases at the time. At least four soldiers had pneumonia, and one died, according to the CDC article.

The virus was identified as an H1N1 swine flu virus, "thought to be a direct descendant of the virus that caused the pandemic of 1918," wrote Krause. "This conclusion was based on antibodies to H1N1 antigens found in survivors of the 1918 pandemic and the belief that the 1918 virus was eventually transmitted to pigs in the Midwest, where it persisted and caused sporadic human cases."

Public health experts, fearing a possible replay of the 1918 pandemic, engaged in an intense debate about how to respond. Eventually they launched a nationwide vaccination campaign, which was announced by President Gerald Ford in March. By the end of the year, 48 million people had been vaccinated, according to an account in Arthur Allen's book Vaccine: The Controversial Story of Medicine's Greatest Lifesaver.

But the feared pandemic never materialized. "The virus is thought to have circulated for a month and disappeared," the CDC article says. "The Fort Dix outbreak may have been an animal anomaly caused by introduction of an animal virus into a stressed human population in close contact in crowded facilities during the winter."

Not only did the pandemic fail to appear, but the vaccine apparently harmed some people. Health officials suspended the vaccination campaign on 16 Dec 1976, after receiving numerous reports of Guillian-Barre syndrome (GBS), a paralyzing neurologic illness, after vaccination, according to an August 1979 report in the American Journal of Epidemiology. Nationwide surveillance detected 1,098 patients with GBS onset from October 1976 through January 1977. Epidemiologic evidence suggested that many cases were related to vaccination, with an estimated risk of 1 case for every 100,000 vaccinations.

Studies of influenza vaccines used after 1976 showed no increased risk for GBS in adults except for borderline statistically significant increases in the 1992-93 and 1993-94 flu seasons, according a report in the Jul 15, 2008, issue of Journal of Infectious Diseases. However, experts still don't know what caused the GBS cases after the swine flu vaccination. One theory was that bacterial antigens from contaminated eggs used in vaccine production could have elicited GBS.

In any case, the episode left the public health establishment demoralized. "The debacle opened public health authorities to the kind of criticism and even ridicule that they had never had to countenance before," wrote Allen.

The concern stirred by this week's report of the two swine flu cases in California readily recalled the 1976 episode. But Marie Gramer, DVM, PhD, a University of Minnesota veterinarian who has studied swine flu, cautioned against drawing many parallels as yet. "It's kind of too early for that," she said. "Certainly in 1976 what got people riled up was that it was adults getting sick. That was outside the norm. This [the California cases] affected children, and children get a lot of influenza."

She said she personally is not overly concerned about the latest cases. "But I think it's important to get this information out there and that people be aware that flu can be shared between humans and pigs," she added.

While influenza is notoriously unpredictable, there is no firm evidence of a swine flu virus having triggered a human flu pandemic, according to multiple reports. The virus that swept around the world in 1918 is believed to have been an avian strain that somehow adapted to humans. The two pandemics since then, in 1957-58 and 1968-69, resulted from genetic reassortment of avian and human strains, though the reassortment could have occurred in an intermediate host such as pigs. No good evidence is available for the many pandemics before 1918.

Most of the flu viruses recently found in pigs have been H1N1 and H3N2 strains, the CDC says. Current swine flu H3N2 viruses are closely related to human H3N2 viruses, because they were introduced into pigs from humans in the late 1990s. But H1N1 swine viruses have been known to circulate in pigs at least since the 1930s.
(CIDRAP 4/22/09)

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Africa
Egypt: Four new human cases of avian influenza H5N1, two deaths
A 25-year-old Egyptian woman has died of the H5N1 bird flu virus, the 25th human fatality and 65th human case of the disease in Egypt, state news agency MENA said on 22 Apr 2009. The woman, from Cairo, died of respiratory failure. Investigations into the source of her infection indicated close contact with sick poultry prior to becoming ill.

On 21 Apr 2009, MENA reported a 6-year old-boy had died from the disease. He resided in Qalyubia governorate and was Egypt's first bird flu fatality of 2009. The boy had been admitted to hospital in late March 2009.

A 33-year-old woman has also contracted bird flu, the 64th recorded case since the first outbreak of the disease in Egypt in 2006, the health ministry announced on 15 Apr 2009. The woman from the Kafr el-Sheikh province of northern Egypt is in critical condition and on an artificial respirator. She first showed symptoms of flu more than a week ago after being exposed to dead fowl thought to have been carrying the disease, the official said.

Additionally, an 18-month-old girl was confirmed the 66th human case of avian influenza H5N1 human infection. She is from Kellin District, Kafr Elsheikh Governorate. Her symptoms began on 15 Apr 2009 and she was hospitalized at Kafr Elsheikh Fever Hospital on 18 Apr 2009, where she was started on oseltamivir on the same day of hospitalization. Her condition is stable. Investigations into the source of infection indicated close contact with dead and sick poultry prior to becoming ill.

Finally, a 4-year-old boy from Sohag governorate has also contracted bird flu and was in hospital. The boy was being treated with the antiviral drug Tamiflu. He is the 67th of bird flu in Egypt, which has been hit harder by bird flu than any other country outside Asia.

Egypt has seen a surge in human cases in recent months, with 16 confirmed since the beginning of 2009, compared to seven cases between 1 Jan and 17 Apr 2008. Most infected Egyptians had come into contact with infected domestic birds in a country where roughly five million households depend on domestically raised poultry as a significant source of food and income. In April 2009, the World Health Organization said it was concerned some Egyptians may carry the bird flu virus without showing symptoms and this could give the virus more of a chance to mutate to a strain that spreads easily among humans.
(ProMED 4/23/09, 4/20/09, 4/17/09)

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2. Updates
AVIAN/PANDEMIC 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. Epidemiological updates on the avian influenza outbreak in Hong Kong available at http://www.oie.int/wahis/public.php?page=single_report&pop=1&reportid=7609 and the outbreak in India at http://www.oie.int/wahis/public.php?page=single_report&pop=1&reportid=7606.
- 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/ Find more than 150 peer-reviewed practices from 25 US states and 37 cities and counties aimed at furthering pandemic preparedness in public health and allied fields.
- 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.
(UN; WHO; FAO, OIE; CDC; CIDRAP; PAHO; USGS)

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3. Articles
Avian influenza at both ends of a migratory flyway: characterizing viral genomic diversity to optimize surveillance plans for North America
Pearce JM et al. Evol Appl. 15 April 2009. Available at http://www3.interscience.wiley.com/cgi-bin/fulltext/122324581/HTMLSTART?CRETRY=1&SRETRY=0.

Abstract
Although continental populations of avian influenza viruses are genetically distinct, transcontinental reassortment in low pathogenic avian influenza (LPAI) viruses has been detected in migratory birds. Thus, genomic analyses of LPAI viruses could serve as an approach to prioritize species and regions targeted by North American surveillance activities for foreign origin highly pathogenic avian influenza (HPAI). To assess the applicability of this approach, we conducted a phylogenetic and population genetic analysis of 68 viral genomes isolated from the northern pintail (Anas acuta) at opposite ends of the Pacific migratory flyway in North America. We found limited evidence for Asian LPAI lineages on wintering areas used by northern pintails in California in contrast to a higher frequency on breeding locales of Alaska. Our results indicate that the number of Asian LPAI lineages observed in Alaskan northern pintails, and the nucleotide composition of LPAI lineages, is not maintained through fall migration. Accordingly, our data indicate that surveillance of Pacific Flyway northern pintails to detect foreign avian influenza viruses would be most effective in Alaska. North American surveillance plans could be optimized through an analysis of LPAI genomics from species that demonstrate evolutionary linkages with European or Asian lineages and in regions that have overlapping migratory flyways with areas of HPAI outbreaks.

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Comparison of the trivalent live attenuated vs. inactivated influenza vaccines among U.S. military service members
Eick AA et al. Virology. 19 April 2009.

Abstract
Limited effectiveness data are available comparing live attenuated influenza vaccine (LAIV) to inactivated influenza vaccine (TIV) among adults. To compare the incidence of influenza-like illness following immunization of adults with LAIV vs. TIV, we conducted a retrospective cohort analysis of active component U.S. military personnel for the 2005–2006 and 2006–2007 influenza seasons. Recruits experienced a much higher burden of disease compared to non-recruits, with crude incidence rates of influenza-like illness 2–16 times higher than non-recruits depending on the season and cohort. For both seasons, a slightly greater protection from influenza-like illness was found for non-recruits who received TIV compared to LAIV (adjusted incidence rate ratio, 1.17 (95% CI, 1.14–1.20) and 1.33 (95% CI, 1.30–1.36), 2005–2006 and 2006–2007 influenza seasons, respectively). However, for Army and Air Force recruits, LAIV was found to provide significantly greater protection from influenza-like illnesses compared to TIV, with adjusted incidence rates of influenza-like illness 22–51% and 18–47% lower among LAIV compared to TIV recipients for the 2005–2006 and 2006–2007 influenza seasons, respectively. Possible reasons for differences in recruit and non-recruit findings include differences in pre-existing influenza antibody levels, differing respiratory disease burden, and/or unmeasured confounding. Consideration of these findings should be made when developing influenza immunization policies.

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Swine Influenza A (H1N1) Infection in Two Children--Southern California, March--April 2009
US Centers for Disease Control and Prevention (CDC). MMWR. 21 Apr 2009; 58(Dispatch); 1-3. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm58d0421a1.htm.

On April 17, 2009, CDC determined that two cases of febrile respiratory illness occurring in children who resided in adjacent counties in southern California were caused by infection with a swine influenza A (H1N1) virus. The viruses from the two cases are closely related genetically, resistant to amantadine and rimantadine, and contain a unique combination of gene segments that previously has not been reported among swine or human influenza viruses in the United States or elsewhere. Neither child had contact with pigs; the source of the infection is unknown. Investigations to identify the source of infection and to determine whether additional persons have been ill from infection with similar swine influenza viruses are ongoing. This report briefly describes the two cases and the investigations currently under way. Although this is not a new subtype of influenza A in humans, concern exists that this new strain of swine influenza A (H1N1) is substantially different from human influenza A (H1N1) viruses, that a large proportion of the population might be susceptible to infection, and that the seasonal influenza vaccine H1N1 strain might not provide protection. The lack of known exposure to pigs in the two cases increases the possibility that human-to-human transmission of this new influenza virus has occurred. Clinicians should consider animal as well as seasonal influenza virus infections in their differential diagnosis of patients who have febrile respiratory illness and who 1) live in San Diego and Imperial counties or 2) traveled to these counties or were in contact with ill persons from these counties in the 7 days preceding their illness onset, or 3) had recent exposure to pigs. Clinicians who suspect swine influenza virus infections in a patient should obtain a respiratory specimen and contact their state or local health department to facilitate testing at a state public health laboratory. (Excerpt.)

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4. Notifications
Influenza in the Asia-Pacific
The Lancet Conferences
Date: August 21-23, 2009
Location: Qingdao, China

The Lancet and The Lancet Infectious Diseases have joined forces to develop a conference that will enable leaders in their fields to present and discuss management of influenza with key health administrators, experts from the medical and scientific communities, and industry representatives. We hope the meeting will provide valuable insight into fundamental public health and operation strategies to bring about change within the Asia-Pacific.

Register now and take advantage of the early bird discount until May 31, 2009. To register, go to http://mail.elsevier-alerts.com/go.asp?/bELA001/qUQEAS8/x8BATS8

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Conference: ICU Infection in an Era of Multi-Resistance
Dates: 4-6 Jun 2009
Location: Chicago, Illinois, USA
Venue: The Palmer House Hilton

Infectious diseases are the second leading cause of death worldwide. In fact, many new and reemerging microbial threats, such as severe acute respiratory syndrome (SARS), avian influenza virus, and West Nile fever continually challenge intensive care providers.

The conference will:
- Discuss infectious disease guidelines for the control and/or prevention of infectious diseases;
- Develop methods/strategies for identifying patients with a potential risk for contracting antibiotic-resistant infections;
- Identify appropriate drug or drug/therapy combinations for combating antibiotic-resistant infections;
- Evaluate hospital and ICU team management strategies for superbugs and foreseeable antibiotic-resistant infections of the future.

Additional information and online registration available at http://www.sccm.org/Conferences/Topics/Summer_Conference/Pages/default.aspx.

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 apecein@u.washington.edu