EINet Alert ~ Jul 03, 2009

***This bulletin was supplemented with information provided by Veratect***

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Economy/ Cases (Deaths)
2009
Australia/ 4090 (7)
Canada/ 7983 (25)
Chile/ 6211 (12)
Mexico/ 8680 (116)
United Kingdom/ 6538 (3)
United States/ 27,717 (127)

Case totals for other APEC economies
Brunei Darussalam/ 29 (0)
China/ 1518 (0)
Indonesia/ 8 (0)
Japan/ 1266 (0)
Korea/ 202 (0)
Malaysia/ 112 (0)
New Zealand/ 711 (0)
Papua New Guinea/ 1 (0)
Peru/ 538 (0)
Philippines/ 861 (1)
Russia/ 3 (0)
Singapore/ 701 (0)
Chinese Taipei/ 61 (0)
Thailand/ 1414 (3)

Map the spread of confirmed pandemic H1N1 influenza at http://www.who.int/csr/don/Map_20090701_1100.png.
(WHO 7/1/09)

Other APEC updates:
Thailand reports its first three H1N1 related deaths; all reportedly had underlying conditions. China report its first H1N1 related death; Japan confirmed its first H1N1 case resistant to antiviral treatment.
(ProMED, 6/27/09, 7/1/09; CIDRAP 7/2/09)

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Cumulative number of human cases of avian influenza A/H5N1
Economy / Cases (Deaths)
2009
China/ 7 (4)
Egypt/ 30 (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 6/30/09)

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 3/23/09):
http://www.who.int/csr/disease/avian_influenza/ai_timeline/en/index.html

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Global: Health officials say antiviral resistance likely in some pandemic H1N1 influenza cases
A spokesman for Roche, the maker of oseltamivir (Tamiflu), said on 29 Jun 2009 that Denmark's report of resistance to the drug in a patient with novel H1N1 influenza, the first reported finding of its kind, wasn't surprising and that the news underscores the importance of monitoring for any viral changes. David Reddy, who leads Roche's influenza task force, said that experts know that during seasonal influenza outbreaks, patients can develop resistance. "We fully expect that this can also occur during treatment with a new flu strain," he said.

He characterized what occurred in the Danish patient as "drug-induced resistance" that developed when a low dose of medication was used, as opposed to the more widespread resistance that occurs when a flu virus acquires new characteristics, which has happened over the past two years with the seasonal H1N1 strain. World Health Organization (WHO) spokesman Dick Thompson said on 30 Jun 2009 that the Danish case is isolated and has no public health implications, Reuters reported. "But we must remain alert as the virus can change at any time and we must not be complacent," he added. The antiviral resistance finding will not prompt any changes in the WHO antiviral recommendations.

Roche said it is monitoring drug resistance in several countries, and officials in several nations, including the United States, are also watching for changes in the virus. The US Centers for Disease Control and Prevention (CDC) said in its most recent surveillance report, released 24 Jun 2009, that of 191 novel H1N1 isolates that have been tested for resistance to neuraminidase inhibitors, none showed resistance.

CDC recommends treatment with oseltamivir or zanamivir for all patients who have confirmed, probable, or suspected novel H1N1 infections who are hospitalized or are at high risk for complications. Carolyn Bridges, associate director of epidemiologic science in the CDC's influenza division, told National Public Radio that though the US hasn't detected any antiviral resistance in the new virus, it will likely occur here eventually. She said the novel flu virus has an "N1" gene that is very different than the "N1" of the seasonal H1N1 virus, so perhaps the pandemic virus isn't as susceptible to the antiviral resistance mutation seen with the seasonal H1N1 strain.
(CIDRAP 6/30/09)

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Global: Studies show novel H1N1 influenza affects deep lung tissue, transmits fairly well
The novel H1N1 influenza now circling the globe causes more serious lung disease than seasonal flu strains and sheds from the lung and throat tissue where it reproduces at higher rates, according to two animal studies published 2 Jul 2009—findings that could explain autopsies and case reports of severe pneumonia as well as the virus's rapid spread. And while the studies, conducted in ferrets and mice, agree that the new flu passes fairly well between individuals, they disagree over the effectiveness of different modes of transmission.

A team from Erasmus Medical Center in the Netherlands found that the virus transmits easily between ferrets housed in cages whose walls are 4 inches apart. But a team from the Massachusetts Institute of Technology (MIT) and the US Centers for Disease Control and Prevention (CDC) found that the novel virus only transmitted well when the ferrets shared direct contact—a sign, the team said, that the new virus has not yet fully adapted to mammals.

The European team, however, warned that the new H1N1 is adapted enough to compete with seasonal flu strains for turf in humans. It "has the ability to persist in the human population, potentially with more severe clinical consequences," they wrote.

Both studies were published online by the journal Science on 2 Jul 2009. The article from Erasmus can be accessed at http://www.sciencemag.org/cgi/content/abstract/1177127. The MIT and CDC study is available at http://www.sciencemag.org/cgi/content/abstract/1177238.
(CIDRAP 7/2/09)

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Andy Burnham, the Health Secretary, said that an almost doubling of cases since 26 Jun 2009 prompted the Government to move to the third and final "treatment" stage of dealing with the outbreak.
(Telegraph 7/3/09)

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More than 1000 infected chickens had been culled between January and May 2009 by local authorities, he said. "We are continuing to collect data based on information from local people whose chickens have died suddenly. The tests on those birds have come back positive for bird flu," he said. The chickens were culled, and their bodies incinerated, he added. Hartono said most of the virus-infected poultry were domestic chickens that were not kept in cages. "Because local villagers traditionally have chickens roaming free, not kept in cages, bird flu has spread very quickly," he said. To curb the virus from spreading further in Purbalingga, the local authorities have set up a special team to combat bird flu."The team is already working 24 hours a day. Any time we receive a report on a dead chicken we will go to the location immediately," Hartono said. The dead chickens, he said, would be used as samples for tests.

Purbalingga has also received 240,000 doses of vaccine from the World Health Organization to help control the spread of bird flu, Hartono said. "Around 30 percent of the vaccines have already been used." The WHO has also provided Purbalingga with anti-bird flu disinfectants. "We have enough medical stocks to deal with bird flu cases. What we need to do more is improve people's awareness so they will keep their poultry cages clean," Hartono said.
(ProMED 6/27/09)

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Indonesia: Announces it will ask foreign visitors to wear masks to guard against pandemic H1N1
Indonesia's health minister said 29 Jun 2009 that visitors arriving at the country's airports from nations hit by novel H1N1 flu will be asked to wear a mask for three days. The masks are a precautionary measure to reduce human-to-human transmission, she said. The masks will be handed out to international visitors as soon as funding for them comes through; however, those who don't wear them will not be penalized.
(CIDRAP 6/30/09)

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Saudi Arabia: Health officials ask groups at high risk for pandemic influenza H1N1 to skip hajj
Saudi Arabian health officials who just concluded a 4-day meeting with international health experts to discuss pandemic flu risks related to the hajj advised that children, pregnant women, elderly people, and those with chronic health conditions avoid the annual pilgrimage on 30 Jun 2009. The 4-day hajj starts in late November 2009 and is expected to attract about 3 million pilgrims. The health ministry said the crowded setting could pose a flu transmission risk.
(CIDRAP 6/30/09)

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Full report available at http://www.defra.gov.uk/animalh/diseases/monitoring/pdf/h1n1-argentina-090626.pdf.

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Argentina: Health minister resigns over handling of novel influenza H1N1 cases
Graciela Ocaña, Argentina’s health minister, resigned 29 Jun 2009 amid a fast-spreading outbreak of novel influenza H1N1 that has killed 26 people in the country, government officials said. Speculation had grown in recent weeks that Ms. Ocaña was considering resigning over differences with the government in the handling of the outbreak and a previous dengue fever outbreak. Argentine news media reported that other cabinet ministers had blocked her proposed measures for handling the epidemics.

In recent days Argentina has reported a disproportionate number of deaths from H1N1 compared to the United States and other countries, a spokesman for the health ministry said. Argentina has reported 26 deaths out of 1,587 infections, or a death rate of 1.6 percent. As a result, Buenos Aires along with five other provinces have declared health emergencies extending school vacations and giving the mayor the power to suspend sports and other entertainment gatherings.
(NY Times 6/29/09; CIDRAP 7/1/09)

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USA: CDC estimates over 1 million Americans infect with pandemic H1N1
Influenza A/H1N1 has infected more than a million Americans, federal health officials said on 26 June 2009, and is infecting thousands more every week even though the annual flu season is well over. That total of those who have already been infected is “just a ballpark figure,” said Dr. Anne Schuchat, director of respiratory diseases at the Centers for Disease Control and Prevention (CDC), adding, “We know we’re not tracking every single one of them.”

Only a tiny fraction of those million cases have been tested, Dr. Schuchat said. The estimate is based on testing plus telephone surveys in New York City and several other locales where the new flu has hit hard. A survey in New York City, she said, showed that almost 7 percent of those called had had flu symptoms during just three weeks in May when the flu was spreading rapidly through schools. If that percentage of the city has had it, then there have been more than 500,000 cases in the city alone, though most have been mild enough that doctors recommended nothing more than rest and fluids.

The flu has now spread to many areas of the country, Dr. Schuchat noted, and the CDC has heard of outbreaks in 34 summer camps in 16 states. About 3,000 Americans have been hospitalized, she said, and their median age is quite young, just 19.

The median age for deaths is somewhat higher, at 37, but that number is pushed up because while only a few elderly people catch the new flu, about 2 percent of them die as a result. Of those who die, Dr. Schuchat said, about three-quarters have some underlying condition like morbid obesity, pregnancy, asthma, diabetes or immune system problems. Even those victims, she said, “tend to be relatively young, and I don’t think that they were thinking of themselves as ready to die.”

The new flu has now reached more than 100 countries, according to the World Health Organization. The world’s eyes are on the Southern Hemisphere, which is at the beginning of its winter, when flu spreads more rapidly. Australia, Chile and Argentina are seeing a fast spread of the virus, mostly among young people, while one of the usual seasonal flus, an H3N2, is also active.

Five American vaccine companies are working on a pandemic H1N1 vaccine, Dr. Schuchat said. The CDC has estimated that once the new vaccine is tested for both safety and effectiveness, no more than 60 million doses will be available by September 2009. That means difficult decisions will have to be made about whom to give it to first.
(NY Times 6/26/09)

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The first case is a one year old boy from Domiat Governorate. His symptoms started on 1 Jun 2009. He was admitted to hospital on 2 Jun 2009, where he received oseltamivir treatment. The patient has recovered and was discharged on 9 Jun 2009.

The second case is a 4 year old girl from Dakhlia Governorate. Her symptoms started on 5 Jun 2009. She was admitted to hospital on 6 Jun 2009, where she received oseltamivir treatment. The patient has recovered and was discharged on 14 Jun 2009.

The 3rd case is a one year old boy from Kaleen District, Kefr El Sheikh Governorate. His symptoms started on 15 Jun 2009. He was admitted to Kefr El Sheikh Fever Hospital on 16 Jun 2009, where he received oseltamivir treatment and is in a stable condition.
(ProMED 7/2/09)

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- WHO
Influenza A/H1N1: http://www.who.int/csr/disease/swineflu/en/index.html
Influenza A/H1N1 frequently asked questions: http://www.who.int/csr/swine_flu/swine_flu_faq_26april.pdf
Map of the spread of influenza A/H1N1: http://www.who.int/csr/don/GlobalSubnationalMaster_20090507_1800.png.

- 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 Canada: http://www.phac-aspc.gc.ca/media/nr-rp/index-eng.php
PAHO: http://www.paho.org/English/AD/DPC/CD/influenza.htm

- 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.
(UN; WHO; FAO, OIE; CDC; CIDRAP; PAHO; USGS)

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Commentary
Influenza A viruses all originate from aquatic birds, which are their natural reservoir. From this vast, ever-present and global source they are able to cross the species barrier and infect a variety of hosts, including humans. Progressive viral adaptation of avian-origin viruses to novel hosts including domesticated birds, pigs, horses, dogs, or humans may result in widespread viral circulation and in the establishment of endemic viruses in a given population. In humans, influenza A infections usually are caused by endemic seasonal viruses and much less frequently by animal influenza viruses that cross the species barrier. A few times each century, some of the animal viruses also gain the capacity to sustain transmission among human populations, resulting in a pandemic. By definition, any emerging pandemic virus will be different antigenically from both human vaccine virus strains and contemporary human viruses, and so the human population will be immunologically naïve to a significant degree to the new virus before it spreads widely. To date, only viruses of the H1, H2, and H3 subtypes are known to have caused pandemics and establish subsequent global circulation.

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“Prepandemic” Immunization for Novel Influenza Viruses, “Swine Flu” Vaccine, Guillain-Barré Syndrome, and the Detection of Rare Severe Adverse Events
Evans D et al. Journal of Infect Dis. 29 Jun 2009; 200:321-328. Available at http://www.journals.uchicago.edu/doi/abs/10.1086/603560.

The availability of immunogenic, licensed H5N1 vaccines and the anticipated development of vaccines against “swine” influenza A(H1N1) have stimulated debate about the possible use of these vaccines for protection of those exposed to potential pandemic influenza viruses and for immunization or “priming” of populations in the so‐called “prepandemic” (interpandemic) era. However, the safety of such vaccines is a critical issue in policy development for wide‐scale application of vaccines in the interpandemic period. For example, wide‐scale interpandemic use of H5N1 vaccines could lead to millions of persons receiving vaccines of uncertain efficacy potentially associated with rare severe adverse events and against a virus that may not cause a pandemic. Here, we first review aspects of the 1976 National Influenza Immunization Programme against “swine flu” and its well‐documented association with Guillain‐Barré syndrome as a case study illustration of a suspected vaccine‐associated severe adverse event in a mass interpandemic immunization setting. This case study is especially timely, given the recent spread of a novel influenza A(H1N1) virus in humans in Mexico and beyond. Following this, we examine available safety data from clinical trials of H5N1 vaccines and briefly discuss how vaccine safety could be monitored in a postmarketing surveillance setting.

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The Persistent Legacy of the 1918 Influenza Virus
Morens DM et al. NEJM. 29 June 2009. Available at http://content.nejm.org/cgi/content/full/NEJMp0904819.

Perspective
It is not generally appreciated that descendents of the H1N1 influenza A virus that caused the catastrophic and historic pandemic of 1918–1919 have persisted in humans for more than 90 years and have continued to contribute their genes to new viruses, causing new pandemics, epidemics, and epizootics. The current international pandemic caused by a novel influenza A (H1N1) virus derived from two unrelated swine viruses, one of them a derivative of the 1918 human virus, adds to the complexity surrounding this persistent progenitor virus, its descendants, and its several lineages. (Excerpt with references removed.)

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Severe Respiratory Disease Concurrent with the Circulation of H1N1 Influenza
Chowell G et al. NEJM. 29 June 2009. Available at http://content.nejm.org/cgi/content/full/NEJMoa0904023.

ABSTRACT
Background In the spring of 2009, an outbreak of severe pneumonia was reported in conjunction with the concurrent isolation of a novel swine-origin influenza A (H1N1) virus (S-OIV), widely known as swine flu, in Mexico. Influenza A (H1N1) subtype viruses have rarely predominated since the 1957 pandemic. The analysis of epidemic pneumonia in the absence of routine diagnostic tests can provide information about risk factors for severe disease from this virus and prospects for its control.

Methods From March 24 to April 29, 2009, a total of 2155 cases of severe pneumonia, involving 821 hospitalizations and 100 deaths, were reported to the Mexican Ministry of Health. During this period, of the 8817 nasopharyngeal specimens that were submitted to the National Epidemiological Reference Laboratory, 2582 were positive for S-OIV. We compared the age distribution of patients who were reported to have severe pneumonia with that during recent influenza epidemics to document an age shift in rates of death and illness.

Results During the study period, 87% of deaths and 71% of cases of severe pneumonia involved patients between the ages of 5 and 59 years, as compared with average rates of 17% and 32%, respectively, in that age group during the referent periods. Features of this epidemic were similar to those of past influenza pandemics in that circulation of the new influenza virus was associated with an off-season wave of disease affecting a younger population.

Conclusions During the early phase of this influenza pandemic, there was a sudden increase in the rate of severe pneumonia and a shift in the age distribution of patients with such illness, which was reminiscent of past pandemics and suggested relative protection for persons who were exposed to H1N1 strains during childhood before the 1957 pandemic. If resources or vaccine supplies are limited, these findings suggest a rationale for focusing prevention efforts on younger populations.

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Pneumonia and Respiratory Failure from Swine-Origin Influenza A (H1N1) in Mexico
Perez-Padila R et al. NEJM. 29 June 2009. Available at http://content.nejm.org/cgi/content/full/NEJMoa0904252.

ABSTRACT
Background In late March 2009, an outbreak of a respiratory illness later proved to be caused by novel swine-origin influenza A (H1N1) virus (S-OIV) was identified in Mexico. We describe the clinical and epidemiologic characteristics of persons hospitalized for pneumonia at the national tertiary hospital for respiratory illnesses in Mexico City who had laboratory-confirmed S-OIV infection, also known as swine flu.

Methods We used retrospective medical chart reviews to collect data on the hospitalized patients. S-OIV infection was confirmed in specimens with the use of a real-time reverse-transcriptase–polymerase-chain-reaction assay.

Results From March 24 through April 24, 2009, a total of 18 cases of pneumonia and confirmed S-OIV infection were identified among 98 patients hospitalized for acute respiratory illness at the National Institute of Respiratory Diseases in Mexico City. More than half of the 18 case patients were between 13 and 47 years of age, and only 8 had preexisting medical conditions. For 16 of the 18 patients, this was the first hospitalization for their illness; the other 2 patients were referred from other hospitals. All patients had fever, cough, dyspnea or respiratory distress, increased serum lactate dehydrogenase levels, and bilateral patchy pneumonia. Other common findings were an increased creatine kinase level (in 62% of patients) and lymphopenia (in 61%). Twelve patients required mechanical ventilation, and seven died. Within 7 days after contact with the initial case patients, a mild or moderate influenza-like illness developed in 22 health care workers; they were treated with oseltamivir, and none were hospitalized.

Conclusions S-OIV infection can cause severe illness, the acute respiratory distress syndrome, and death in previously healthy persons who are young to middle-aged. None of the secondary infections among health care workers were severe.

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Historical Perspective--Emergence of Influenza A (H1N1) Viruses
Zimmer SM. NEJM. 29 June 2009. Available at http://content.nejm.org/cgi/content/full/NEJMra0904322.

On April 17, 2009, officials at the Centers for Disease Control and Prevention (CDC) confirmed two cases of swine influenza in children living in neighboring counties in California. Here we take a perspective from systems biology to review the series of evolutionary and epidemiologic events, starting in 1918, that led to the emergence of the current swine-origin influenza A (H1N1) strain (S-OIV), which is widely known as swine flu. This article is one of two historical articles on influenza A (H1N1) viruses in this issue of the Journal. Our review focuses on the key steps that characterize this viral evolution. (Excerpt with references removed.)

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Spread of a Novel Influenza A (H1N1) Virus via Global Airline Transportation
Kahn K et al. NEJM. 29 June 2009. Available at http://content.nejm.org/cgi/content/full/NEJMc0904559.

Correspondence
To the Editor: Throughout March and April 2009, international air travelers departing from Mexico were unknowingly transporting a novel influenza A (H1N1) virus to cities around the world. We analyzed the flight itineraries for all passengers departing from commercial airports in Mexico between March and April 2008, using data from the International Air Transport Association (IATA). The purpose of this analysis was to show how travelers — and consequently to predict how H1N1 — would disseminate worldwide during the initial wavefront of this epidemic. We analyzed IATA data from March and April 2008 for the following reasons: the data accounted for more than 95% of all passenger trips worldwide via commercial airlines, they included information on the flight origins and destinations of actual passengers, data on passenger itineraries for the period from March through April 2009 were unavailable at the time of this analysis, the global pattern of passenger departures from Mexico between March and April varies minimally from year to year, and the epidemic in Mexico was largely unrecognized during the period from March through April 2009, with passenger departures presumably following their usual seasonal pattern. (Excerpt.)

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Weekly Epidemiological Record Bulletin
WHO. 19 June 2009; 84(25): 249-260. Available at http://www.who.int/wer.

Contents include:
New influenza A (H1N1) virus: global epidemiological situation, June 2009

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US CDC and FDA Emergency Use Authorization Course
Interactive module pertaining to utilizing and accessing the national stockpile developed by the US Centers for Disease Control and Prevention (CDC) and the US Federal Drug Administration (FDA).

Now available online at http://emergency.cdc.gov/training/eua/index.html.

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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.

To register, go to http://mail.elsevier-alerts.com/go.asp?/bELA001/qUQEAS8/x8BATS8

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