EINet Alert ~ Aug 29, 2008

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2008
Bangladesh / 1 (0)
China / 3 (3)
Egypt / 7 (3)
Indonesia / 18 (15)
Viet Nam / 5 (5)
Total / 34 (26)

***For data on human cases of avian influenza prior to 2008, go to: http://depts.washington.edu/einet/humanh5n1.html

Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 385 (243).
(WHO 6.19.08 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 6.19.08)

WHO's maps showing world's areas affected by H5N1 avian influenza (last updated 8.18.08): http://gamapserver.who.int/mapLibrary/

WHO’s timeline of important H5N1-related events (last updated 8.14.08): http://www.who.int/csr/disease/avian_influenza/ai_timeline/en/index.html

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Global: Researchers say oseltamivir resistance becoming more prevalent   PRINT THIS EMAIL THIS
Tamiflu [oseltamivir] resistant forms of the "ordinary" seasonal influenza are rapidly spreading and the drug may be ineffective in fighting the dominant flu strain in South Africa this winter [2008-2009]. World Health Organisation (WHO) data show tests on 107 people in South Africa with the H1N1 strain, one of the three most common flu viruses in humans, found all had a mutant [virus] resistant to Tamiflu. Only one patient was taking Tamiflu at the time. Tests on 788 samples taken from H1N1 flu patients in 12 countries, mostly in the southern hemisphere, from 1 Apr to 20 Aug 2008 found that 242, or 31 percent, had the H274Y mutation [in the neuraminidase protein gene] associated with Tamiflu resistance, WHO said. Southern hemisphere incidence of the mutation in tests on the H1N1 virus ranged from 100 percent in South Africa to 13 percent in Chile, compared with a resistance rate of 16 percent found in 7,528 samples tested from the last quarter of 2007 to 31 Mar 2008 in 34 countries, mostly in the northern hemisphere. "What we're seeing is the [spread] of the resistance gene and the distribution of it throughout the world," said Lance Jennings, a clinical virologist with the Canterbury District Health Board [New Zealand], who is chairman of the Asia-Pacific Advisory Committee on Influenza. "We have a lot to learn about the molecular epidemiology of influenza viruses." The Tamiflu-resistant form of flu has been reported in 40 countries in Europe, North and South America, Africa, Asia, and Australia since widespread resistance to the drug was first reported to the WHO by Norway in January 2007.

Until bird flu vaccines are developed for the specific pandemic influenza virus once it evolves and starts spreading, work likely to take three months or more, Tamiflu and another retroviral treatment, Relenza, are the main medical weapons to battle pandemic flu. Tamiflu is being stockpiled by WHO and governments around the world for use in the event of a pandemic, and to treat the H5N1 avian flu strain that has infected humans in 15 of the 60 countries to which it has spread.

In 2007, Swedish researchers warned that sewage systems do not break down Tamiflu, and that the drug was being discharged in rivers and streams used by the waterfowl thought to be the main carriers of avian flu. They urged doctors not to over-prescribe Tamiflu to avoid creating resistance in avian flu carried by ducks. If those viruses combined with other viruses that made humans sick they could mutate into strains resistant to Tamiflu, they said early in 2007. (ProMED 8/25/08)

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The H5N1 outbreak that broke out in West Bengal in January 2008 spread to nearly 13 of the state's 19 districts. An animal husbandry department source stated: "Both India and Bangladesh finally exchanged genetic information of its H5N1 strains. We have found that both the strains are related. However, we can't say that Bangladesh was the cause of the outbreak in West Bengal because we don't have documented proof to show that infected poultry was smuggled into India." He added: "We now know that both the viruses were of clade 2.2 variety which is a sub-lineage of the highly pathogenic Qinghai strain. The strain, however, is different to the one that caused the Manipur and Maharashtra outbreaks."

India was almost certain that the virus came from Bangladesh through illegal poultry trade. Even agriculture minister Sharad Pawar had openly said so. The animal husbandry department then made a formal request to the Bangladesh government through the ministry of external affairs to share the genetic history of its virus. The H5N1 virus was first detected in Bangladesh in March 2007. Since then, over 47 of the country's 64 districts had been affected by bird flu.
(Times of India 8/26/08)

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Japan: Sharp Corp's air purifier could be valuable weapon in the fight against H5N1 avian influenza   PRINT THIS EMAIL THIS
Japan's Sharp Corp. said that it has developed an air purifier that eliminates 99.9 percent of the virulent H5N1 strain of bird flu within 10 minutes. The system has been improved from an earlier version which was shown in 2005 to have eliminated 99 percent of the H5N1 virus when airborne, Sharp official Kenji Ota said. The plasmacluster ion technology, developed in 2000, disables airborne micro-organisms by releasing positive and negative ions into the air. Direct contact with infected poultry, or surfaces contaminated by their feces, is currently considered the main cause of human infection with the H5N1 virus, according to the World Health Organization.

But influenza is a hard virus to beat and will need several lines of defense, said John Oxford, a University of London professor who heads Retroscreen Virology, a British research institute involved in the project. "This kind of new technology will add something to (our) ammunition box," he said. Plasmacluster ions have also proved effective against 26 other kinds of harmful airborne substances, including bacteria and allergens, Sharp said. During the tests, the H5N1 virus was sprayed in a one-cubic meter box with a concentration of 50,000 ions per cubic centimeter. Samples were then taken 10 minutes later and injected into cell cultures.

Plasmacluster technology can be installed in air conditioners, dehumidifiers and air purifiers for home and industrial use, although Sharp gave no indication of when the latest technology might be used commercially. Sanyo Electric Co. has also developed a similar technology that proved 99 percent efficient in removing the bird flu virus using electrolyzed tap water.
(AFP 8/27/08)

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Viet Nam: Unusual strain of H5N1 avian influenza virus starting to appear in smuggled poultry   PRINT THIS EMAIL THIS
Agriculture officials in Viet Nam said on 27 Aug 2008 that an unusual strain of H5N1 virus is starting to appear in smuggled poultry, the Vietnam News Agency (VNA) reported. Bui Quang Anh, head of the agriculture ministry's animal health department, said that the strain poses a high risk of infecting humans and had previously caused an outbreak in China. Anh said that the H5N1 strain was named "seven." The story did not mention a clade number. Typically, the story said, "strain one" of the H5N1 virus has infected birds in the Mekong delta, while strains two, three, and four have been found to infect birds in the country's Red River Basin. Nguyen Van Cam, director of Vietnam's Central Animal Diagnosis Centre, said the lab was doing more tests to better characterize the strain and that he expected results soon.
(CIDRAP 8/28/08)

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Many large multinational biotechs -- GlaxoSmithKline, Sanofi-Aventis, Novartis -- are working on bird flu vaccines in the United States and Western Europe under government contract, said Ken Trbovich, an analyst with RBC Capital Markets. Novavax has partnered with GE Healthcare to reach the rest of the world by providing other countries a system to quickly mass-produce vaccines. "If you truly believe a pandemic outbreak is likely, there is reason to believe foreign governments and the U.S. will clamp down and control the supply," Trbovich said. He added, "Other places in the world may have a lot of money, but no amount of money will get you vaccines in the case of a pandemic."

Traditionally, to create flu vaccines, drugmakers grow live virus strains in chicken eggs, which act as incubators. The virus is later killed and bottled into a vaccine. But eggs are a volatile medium, and a scarce supply essentially stops production. Novavax's bird flu vaccine uses particles that mimic the size and shape of the virus, which trigger an immune response but lack the genetic material to replicate. Because the particles are produced in more stable insect-cell cultures, yields are seven to 10 times higher than egg-based manufacturing, Novavax said. The vaccine can also be created within 10 to 12 weeks of identifying a pandemic strain -- half the time it takes to make egg-based vaccines.

GE is developing the production equipment, which is cheap to set up and run in case of a pandemic. In December 2007, Novavax studied low doses of its bird flu vaccine in a much smaller patient population. After tweaking the production process, the biotech was able to elicit a stronger immune response in this recent trial. Novavax is seeking a governmental or pharmaceutical partner to finance the next set of human trials. "We see no reason to invest additional money of our own into the pandemic vaccine when we can wait for a foreign government that needs this vaccine to put money in," Singhvi said. Meanwhile, Novavax will begin human tests of its seasonal influenza vaccine, using virus-like particles, in the fall. Currently all U.S. flu vaccines are egg-based. "The pandemic area is difficult to monetize even if you successfully generate a contract," Trbovich said. "There are no reoccurring revenues. Moving a seasonal flu vaccine into clinical trials is their first real commercial opportunity."
(Washington Post 8/27/08)

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USA: University of Pittsburg receives $3.6 million for avian influenza vaccine research   PRINT THIS EMAIL THIS
Monkeys and viral decoys could be key to creating an effective avian-flu vaccine before a pandemic can strike. The National Institutes of Health has awarded the University of Pittsburgh Center for Vaccine Research a $3.6 million grant to conduct animal studies on a vaccine the center designed to protect against the most common and deadliest strain of avian flu. Recent avian-flu outbreaks in Africa, Asia and Europe, with expectations the H5N1 strain soon could arrive in North America, have prompted officials to warn of a potential pandemic. Worldwide, more than 200 cases of avian flu in humans have been documented.

Ted Ross, principal investigator in the vaccine development project and assistant professor at Pitt, said the grant will allow the team to test the vaccine on monkeys in the center's 20,000-square-foot Regional Biocontainment Laboratory. It marks the first time monkeys will be used in vaccine development. If the vaccine proves effective in the monkeys, it could be ready for human trials within three years. "Our goal is to move it into human studies," Dr. Ross said. "What's nice about our work, in looking at H5N1, there are numerous subtypes it could cause. We could quickly respond and quickly make vaccines."

Pitt is using a relatively new approach in developing its avian-flu vaccine. Typically vaccines are produced with live viruses, but the center is using a virus-like particle that the immune system still perceives to be the real virus. The viral decoy is safer because it does not include its genome or "bad parts of the virus," Dr. Ross said. That speeds up the manufacturing process and reduces costs. Gardasil, the vaccine against viruses that cause cervical cancer, was the first to use virus-like particles to be approved by the U.S. Food and Drug Administration. Given the evolving nature of H5N1, the new vaccine also is being engineered to encode genes for many influenza viral proteins, which will enhance protection against possible new strains of avian flu. "If there's a different strain, we quickly can make a vaccine," Dr. Ross said.
(Pittsburg Post-Gazette 8/27/08)

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About 10 years ago, Professor Robert M. Krug at The University of Texas at Austin discovered that the NS1 protein binds a human protein known as CPSF30, which is important for protecting human cells from flu infection. Once bound to NS1, the human protein can no longer generate molecules needed to suppress flu virus replication. Now, researchers led by Rutgers Professor Gaetano T. Montelione and Krug identified the novel NS1 binding pocket that grasps the human CPSF30 protein. "Our work uncovers an Achilles heel of influenza A viruses that cause human epidemics and high mortality pandemics," said Montelione, professor of molecular biology and biochemistry. "We have identified the structure of a key target site for drugs that could be developed to effectively combat this disease." X-ray crystallography, which was carried out by Kalyan Das, Eddy Arnold, LiChung Ma and Montelione, identified the three-dimensional structure of the NS1 binding pocket. "The X-ray crystal structure gives us unique insights into how the NS1 and human protein bind at the atomic level, and how that suppresses a crucial antiviral response," said Das, research professor at Rutgers.

Rei-Lin Kuo, Jesper Marklund, Karen Twu and Krug at The University of Texas at Austin verified the key role of this binding pocket in flu replication by genetically engineering a change to a single amino acid in the NS1 protein's binding pocket, which in turn eliminated the protein's ability to grasp the human protein that is needed to generate antiviral molecules. These investigators then produced a flu virus with an NS1 pocket mutation and showed that this mutated virus does not block host defenses, and as a consequence has a greatly reduced ability to infect human cells. "These experiments validate the NS1 pocket as a target for antiviral drug discovery," said Krug, professor and chair of molecular genetics and microbiology. "Because this NS1 pocket is highly conserved in all influenza A viruses isolated from humans, a drug targeted to the pocket would be effective against all human influenza A strains, including the bird flu."
(Science Daily 8/26/08)

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Influenza A virus infections in land birds, People’s Republic of China   PRINT THIS EMAIL THIS
Townsend PA, et al. Emerging Infectious Diseases. 2008 Oct; [Epub ahead of print]. http://www.cdc.gov/eid/content/14/10/pdfs/08-0169.pdf

Introduction
Avian influenza virus ecology has long regarded waterbirds as a primary reservoir. Although the benchmark study detailed prevalences across all taxa, subsequent studies have focused exclusively on waterbirds with few exceptions. We reexamined these assumptions on the basis of a broad sampling of bird diversity in Southeast Asia, where bird-borne influenza viruses are of particular concern. We sampled and tested diverse land birds for influenza A virus infection and showed that land birds also harbor infections with these viruses. Birds in these taxa are not irrelevant in virus transmission and should form an integral part of avian influenza surveillance and monitoring programs.
(CIDRAP 8/29/09)

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Evidence of Infection by H5N2 Highly Pathogenic Avian Influenza Viruses in Healthy Wild Waterfowl   PRINT THIS EMAIL THIS
Gaidet N, et al. PloS Pathog. 2008;4(8):e1000127 http://www.plospathogens.org/article/info%3Adoi%2F10.1371/journal.ppat.1000127

Abstract
The potential existence of a wild bird reservoir for highly pathogenic avian influenza (HPAI) has been recently questioned by the spread and the persisting circulation of H5N1 HPAI viruses, responsible for concurrent outbreaks in migratory and domestic birds over Asia, Europe, and Africa. During a large-scale surveillance programme over Eastern Europe, the Middle East, and Africa, we detected avian influenza viruses of H5N2 subtype with a highly pathogenic (HP) viral genotype in healthy birds of two wild waterfowl species sampled in Nigeria. We monitored the survival and regional movements of one of the infected birds through satellite telemetry, providing a rare evidence of a non-lethal natural infection by an HP viral genotype in wild birds. Phylogenetic analysis of the H5N2 viruses revealed close genetic relationships with H5 viruses of low pathogenicity circulating in Eurasian wild and domestic ducks. In addition, genetic analysis did not reveal known gallinaceous poultry adaptive mutations, suggesting that the emergence of HP strains could have taken place in either wild or domestic ducks or in non-gallinaceous species. The presence of coexisting but genetically distinguishable avian influenza viruses with an HP viral genotype in two cohabiting species of wild waterfowl, with evidence of non-lethal infection at least in one species and without evidence of prior extensive circulation of the virus in domestic poultry, suggest that some strains with a potential high pathogenicity for poultry could be maintained in a community of wild waterfowl.
(Resource Guide for Public Health Preparedness 8/15/08)

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Genotypic diversity of H5N1 highly pathogenic avian influenza viruses   PRINT THIS EMAIL THIS
Zhao Z-M, et al. Journal of General Virology. 2008;89:2182-2193 http://vir.sgmjournals.org/cgi/content/abstract/89/9/2182

Abstract
Besides enormous economic losses to the poultry industry, recent H5N1 highly pathogenic avian influenza viruses (HPAIVs) originating in eastern Asia have posed serious threats to public health. Up to April 17, 2008, 381 human cases had been confirmed with a mortality of more than 60 %. Here, we attempt to identify potential progenitor genes for H5N1 HPAIVs since their first recognition in 1996; most were detected in the Eurasian landmass before 1996. Combinations among these progenitor genes generated at least 21 reassortants (named H5N1 progenitor reassortant, H5N1-PR1–21). H5N1-PR1 includes A/Goose/Guangdong/1/1996(H5N1). Only reassortants H5N1-PR2 and H5N1-PR7 were associated with confirmed human cases: H5N1-PR2 in the Hong Kong H5N1 outbreak in 1997 and H5N1-PR7 in laboratory confirmed human cases since 2003. H5N1-PR7 also contains a majority of the H5N1 viruses causing avian influenza outbreaks in birds, including the first wave of genotype Z, Qinghai-like and Fujian-like virus lineages. Among the 21 reassortants identified, 13 are first reported here. This study illustrates evolutionary patterns of H5N1 HPAIVs, which may be useful toward pandemic preparedness as well as avian influenza prevention and control.
(CIDRAP 8/26/08)

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Clinical Characteristics of 26 Human Cases of Highly Pathogenic Avian Influenza A (H5N1) Virus Infection in China   PRINT THIS EMAIL THIS
Yu H, et al. PLoS ONE 2008;3(8): e2985. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0002985

Background
While human cases of highly pathogenic avian influenza A (H5N1) virus infection continue to increase globally, available clinical data on H5N1 cases are limited. We conducted a retrospective study of 26 confirmed human H5N1 cases identified through surveillance in China from October 2005 through April 2008.

Methodology/Principal Findings
Data were collected from hospital medical records of H5N1 cases and analyzed. The median age was 29 years (range 6–62) and 58% were female. Many H5N1 cases reported fever (92%) and cough (58%) at illness onset, and had lower respiratory findings of tachypnea and dyspnea at admission. All cases progressed rapidly to bilateral pneumonia. Clinical complications included acute respiratory distress syndrome (ARDS, 81%), cardiac failure (50%), elevated aminotransaminases (43%), and renal dysfunction (17%). Fatal cases had a lower median nadir platelet count (64.5×109 cells/L vs 93.0×109 cells/L, p = 0.02), higher median peak lactic dehydrogenase (LDH) level (1982.5 U/L vs 1230.0 U/L, p = 0.001), higher percentage of ARDS (94% [n = 16] vs 56% [n = 5], p = 0.034) and more frequent cardiac failure (71% [n = 12] vs 11% [n = 1], p = 0.011) than nonfatal cases. A higher proportion of patients who received antiviral drugs survived compared to untreated (67% [8/12] vs 7% [1/14], p = 0.003).

Conclusions/Significance
The clinical course of Chinese H5N1 cases is characterized by fever and cough initially, with rapid progression to lower respiratory disease. Decreased platelet count, elevated LDH level, ARDS and cardiac failure were associated with fatal outcomes. Clinical management of H5N1 cases should be standardized in China to include early antiviral treatment for suspected H5N1 cases.
(CIDRAP 8/22/08)

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Evolutionary and Transmission Dynamics of Reassortant H5N1 Influenza Virus in Indonesia   PRINT THIS EMAIL THIS
Lam TT-Y, et al. PLoS Pathog. 2008;4(8): e1000130. http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000130

Abstract
H5N1 highly pathogenic avian influenza (HPAI) viruses have seriously affected the Asian poultry industry since their recurrence in 2003. The viruses pose a threat of emergence of a global pandemic influenza through point mutation or reassortment leading to a strain that can effectively transmit among humans. In this study, we present phylogenetic evidences for the interlineage reassortment among H5N1 HPAI viruses isolated from humans, cats, and birds in Indonesia, and identify the potential genetic parents of the reassorted genome segments. Parsimony analyses of viral phylogeography suggest that the reassortant viruses may have originated from greater Jakarta and surroundings, and subsequently spread to other regions in the West Java province. In addition, Bayesian methods were used to elucidate the genetic diversity dynamics of the reassortant strain and one of its genetic parents, which revealed a more rapid initial growth of genetic diversity in the reassortant viruses relative to their genetic parent. These results demonstrate that interlineage exchange of genetic information may play a pivotal role in determining viral genetic diversity in a focal population. Moreover, our study also revealed significantly stronger diversifying selection on the M1 and PB2 genes in the lineages preceding and subsequent to the emergence of the reassortant viruses, respectively. We discuss how the corresponding mutations might drive the adaptation and onward transmission of the newly formed reassortant viruses.
(CIDRAP 8/22/08)

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Dates: 18-19 September 2008
Location: Seattle, WA, USA
Venue: Bell Harbor International Conference Center

PHI2008 will be hosted by Global Partners in Public Health Informatics (GPPHI) at the Center for Public Health Informatics (CPHI) at the University of Washington, Seattle, WA, USA. The idea of creating a partnership of governmental and non-governmental organizations, academic institutions and companies to define and develop a vision for addressing health challenges in low-resource settings through information and communications technologies was first articulated at PHI2007: Building a Global Partnership in Public Health Informatics. PHI2007 brought together nearly 200 individuals from across the globe who created the impetus for the Global Partners in PHI.

The Rockefeller Foundation recently funded the UW Center for Public Health Informatics to begin the planning process for the Global Partners organization. That process will take place over the coming year through an invitational meeting on Public Health Informatics at the Rockefeller Foundation conference center in Bellagio, Italy as well as at the second annual GPPHI meeting -- PHI2008 -- to be held in September 18-19, 2008 at the Bell Harbor Conference Center, Seattle, Washington, USA. The theme for the PHI2008 meeting is "Envisioning Options for Integrated Public Health Information Systems for Low Resource Settings: Components, Connections, Partners, Strategies."

Program:
- Keynote addresses by leading international experts

- Plenary presentations:
- National approaches from countries leading the development of integrated public health information systems
- Creative approaches to collecting and linking data and systems to improve public health practice
- Strategies for compiling and delivering contextually relevant information for decision support
- Poster sessions presenting research and applied methodologies and results from public health informatics interventions in low-resource settings throughout the world

- Panelist discussions of funding opportunities for research and applications development

- Information exchange and networking opportunities

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The 7th International Bird Flu Summit   PRINT THIS EMAIL THIS
http://www.new-fields.com/birdflu7/

November 13-14, 2008 in Las Vegas, Nevada. The two-day event will draw on first-hand best practices to create solid business continuity plans that companies and organizations need to prepare for, respond to, and survive a pandemic. Public Health Officials, Top leaders and key decision-makers of major companies representing a broad range of industries will meet with distinguished scientists, law enforcers, first responders, and other experts to discuss pandemic prevention, preparedness, response and recovery at the two day summit.

Discussions topics:
* Surveillance and Data Management
* Preparing Communities Strategies; Local Partnership and Participation
* Delivery of Vaccine and Antiviral Medication
* National Pandemic Influenza Medical Countermeasure
* Socio Economic Impact on Poultry Industry
* Benefit-risk Assessment: Public Health, Industry and Regulatory Perspectives
* Prevention Education Efforts and Risk Communication
* Command, Control and Management
* Emergency Response Management
* Business-Based Planning
* School-Based Planning
* Community-Based Planning and more!

New Fields
1001 Pennsylvania Avenue, NW
6th Floor South
Washington, DC 20004
Tel: (202) 536-5000; Fax: 202.280.1239; email: sharon.villalon@new-fields.com

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No Ordinary Flu: Preparedness comic book in multiple languages   PRINT THIS EMAIL THIS
http://www.metrokc.gov/health/pandemicflu/comicbook.htm
To promote pandemic flu preparedness, Public Health - Seattle & King County has developed a 12-page comic book on pandemic flu. Targeting readers of all ages, this story tells the tale of a family’s experience of the 1918 influenza pandemic. It also explains the threat of pandemic flu today, illustrates what to expect during a pandemic (such as school closures), and offers tips to help households prepare. You can order copies (or download) all 12 language versions of the comic (PDF format) at the above link.

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