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Vol. XII, No. 7 ~ EINet News Briefs ~ Apr 03, 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)
- India (West Bengal): 14,000 birds to be culled due to avian influenza infection
- Indonesia: Deceased toddler confirmed to have died of avian influenza H5N1
- Indonesia: Suspected avian influenza H5N1 cases in Garut and Karawang districts
- Egypt: Children are country’s 60th and 61st cases of avian influenza H5N1

2. Infectious Disease News
- Australia (New South Wales): One person at source of cryptosporidium outbreak
- Australia (Northern Territory): Man dies of Murray Valley encephalitis
- Australia (Pilbarra): Bat bite sparks health warning
- China (Shandong): Thousands of children ailed by hand-foot-mouth disease
- Chinese Taipei: Angiostrongylus in Thai workers after consuming raw snails
- Indonesia: 200 residents diagnosed with chikungunya virus
- Indonesia (Bali): Two more fatalities in rabies outbreak
- USA: FDA approves new vaccine to prevent Japanese encephalitis
- USA (Arizona): State veterinarian urges precautions due to large rabies outbreak
- USA (Hawaii): Two rat lungworm patients recovering
- USA (Tennessee): Ten colonoscopy patients diagnosed with hepatitis

3. Updates
- AVIAN/PANDEMIC INFLUENZA
- DENGUE

4. Articles
- Influenza Virus Resistance to Antiviral Agents: A Plea for Rational Use
- DNA vaccination protects against an influenza challenge in a double-blind randomised placebo-controlled phase 1b clinical trial
- Avian influenza virus (H5N1): effects of physico-chemical factors on its survival
- A comparison of the pathogenicity of avian and swine H5N1 influenza viruses in Indonesia
- Estimation of Influenza Vaccine Effectiveness from Routine Surveillance Data
- Use of Unstructured Event-Based Reports for Global Infectious Disease Surveillance
- Conventional and future diagnostics for avian influenza
- Highly pathogenic H5N1 avian influenza virus: Cause of the next pandemic?

5. Notifications
- APEC Conference for the Surveillance, Treatment, Laboratory Diagnosis and Vaccine Development of Enteroviruses
- Health Sciences Online has launched
- APEC EINet director to attend WHO meeting on outbreak response coordination
- Introducing the Journal of Bacteriology Research
- Researchers launch online vector database
- CDC Symposium on Drug-resistant and Vaccine-escape HBV Mutants


1. Influenza News

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

2009
China/ 7 (4)
Egypt/ 9 (0)
Viet Nam/ 2 (2)
Total/ 18 (6)

***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: 413 (256).
(WHO 3/30/09 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 3/11/09)

WHO's maps showing world's areas affected by H5N1 avian influenza (last updated 3/18/09): 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
India (West Bengal): 14,000 birds to be culled due to avian influenza infection
North Dinajpur district administration has decided to cull around 14,000 birds in several villages under Daspara and Ghinnigaon gram panchayats (villages) by 3 Apr 2009. The decision followed the official announcement declaring the block as bird flu affected. It was reported that hundreds of birds died in the region since 24 Mar 2009, alarming the district administration. The North Dinajpur animal husbandry department officials promptly visited the affected villages and collected samples from the dead birds, which were later sent to a national laboratory. The laboratory report confirmed bird flu in the area.
(ProMED 3/30/09)

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Indonesia: Deceased toddler confirmed to have died of avian influenza H5N1
Blood samples taken from the two-and-a-half-year-old child who died during the week of 23-27 Mar 2009 in Pekanbaru, Riau, have tested positive for the bird flu virus, an official said on 1 Apr 2009. Azizman Saad, coordinator of the bird flu prevention team at the Arifin Ahmad hospital in Pekanbaru, said that confirmation that the child died from bird flu had been received by the Riau Health Office several days ago.

"The victim is believed to have contracted the virus from dead chickens in his surrounding areas," Azizman stated. Indonesia's bird flu total death toll reached 119 as of early March 2009, according to data from the national bird flu commission. Blood samples of patients believed to have been infected with the virus are usually sent to the Health Research Agency of the Ministry of Health in Jakarta.

Following the confirmation, Azizman urged the child's family members and neighbors in Tanjung Rhu village, Pekanbaru to go to the nearest community health center to have a check-up. "There has not been any evidence that the bird flu infection can be transmitted from human to human, but the case shows the bird flu outbreak took place in the victim's area. It's better for those who had made contact with the victim to go to the health center even though they do not have any health problems," he said.

Azizman explained that the child was intensively treated for high fever and coughing and breathing difficulties in an isolated room at Arifin Achmad hospital. "One day before he died, his condition was improving but, finally, his condition deteriorated and he fell unconscious. Six doctors tried to save his life, but to no avail," he said. Azizman explained that before the disclosure of the laboratory tests the child was believed to have died from multi-organ failure.

Rini Hermiyati of the Pekanbaru Health Office said she had assigned a team to observe the health condition of the victim's family members and at the same time make an inventory of neighbors who were in contact with the victim. "No one has been found with symptoms of bird flu, but those having contact with the victims will be closely watched out for 21 days," Rini said.

The Pekanbaru Livestock Husbandry Office made the decision to cull chickens in the areas surrounding the victim’s residence to help curb the spread of the virus. "The number of chickens raised here is small," she said. Meanwhile, Susi Herlinda, a member of the Pekanbaru Legislative Council, criticized the administration for its failure to anticipate the bird flu infection. The death of the victim showed the administration was not aggressive enough in campaigning about the dangers of bird flu, she said. "It has become a habit of our people, everybody acts only after somebody falls victim to a certain diseases. The death of this child should have been used as momentum to improve," she said. "Related institutions have to create awareness among the public about the danger of the bird flu," Susi added.
(ProMED 4/2/09)

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Indonesia: Suspected avian influenza H5N1 cases in Garut and Karawang districts
The Garut Health Service has recorded 46 cases of bird flu in Garut District up to 23 Mar 2009 since the beginning of the outbreak in Indonesia in 2005. The 46 cases include one surviving bird flu patient, four dead bird flu victims, 36 surviving bird flu suspects and five dead bird flu suspects, Dr Hendy Budiman, head of the Garut health service, said on 26 Mar 2009.

The district health authorities even found two new bird flu suspects in Cintanagara village, Cigedug sub district, recently, he said. The two bird flu suspects were currently being treated at a local hospital and their condition was improving, he said. The new patients were a 30-year-old woman and her 35-year-old sister from Tabrik Lebak Cintamaya kampong (village). Around 50 chickens died suddenly in the village of the patients, he said, adding that his office was currently investigating the sudden death of the chickens.

Meanwhile, a 50-year-old female resident of Karawang District is suspected to have contracted bird flu virus. The victim was admitted to Hasan Sadikin hospital on 29 Mar 2009. According to the patient's 40-year-old wife, her husband developed fever and breathing difficulty signs. He was brought to Ramerta clinic and then directed to the Dewi Sri clinic. The patient's wife said that the doctor at Dewi Sri clinic told her that her husband has developed bird flu symptoms, but the diagnosis still had to be confirmed.

During the past two weeks a number of chickens were found suddenly dead in the victim's area. "My husband is the only one who developed symptoms," she added.
(ProMED 3/28/09, ProMED 3/31/09)

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Africa
Egypt: Children are country’s 60th and 61st cases of avian influenza H5N1
The Egyptian Ministry of Health and Population announced on 28 Mar 2009 that a two-year-old baby girl has contracted highly pathogenic avian H5N1 influenza virus infection, the 60th case in Egypt since the beginning of 2006. The victim is from Qena District, Qena Governorate. Her symptoms began on 23 Mar 2009 and she was admitted to Qena Fever Hospital on 24 Mar 2009 where she was started on oseltamivir treatment the same day and remains in a stable condition.

Infection with H5N1 avian influenza was confirmed by the Egyptian Central Public Health Laboratory on 26 Mar 2009 and recognized by WHO on 30 Mar 2009. Investigations into the source of infection indicate a history of close contact with dead and sick poultry prior to becoming ill.

In addition, a 2-year-old Egyptian boy has contracted the highly pathogenic bird flu virus, bringing to 61 the number of confirmed cases in the country, state news agency MENA said 1 Apr 2009. The boy, from the province of Beheira in northern Egypt, is believed to have contracted the virus after coming into contact with infected birds, health ministry spokesman Abdel Rahman Shahine said. The boy was taken to hospital on 30 Mar 2009 after he came down with a high fever while visiting extended family in another province. He was being treated with the antiviral drug Tamiflu.

Avian influenza has caused the deaths of 23 persons in Egypt, predominantly young females and adult women, who are mainly responsible for the rearing of domestic poultry in rural areas. Despite considerable effort, the authorities have been unable to alter the habits of the population, who, in large part, follow the habits of their ancestors in keeping their poultry on the roofs of their houses.

The Ministry spokesman stated that the avian influenza death toll in Egypt had been lower than in some other countries affected by the disease. The World Health Organization (WHO) has recently initiated an inquiry into the reason for the apparent increased susceptibility of young children to this virus infection. In October 2008, an international conference on avian influenza was held in Egypt, during the course of which Washington allocated USD 320 million to fight this disease.
(ProMED 3/29/09, 3/30/09, 4/2/09)

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2. Infectious Disease News

Asia
Australia (New South Wales): One person at source of cryptosporidium outbreak
Genetic testing has revealed that Sydney's cryptosporidium outbreak may have stemmed from a single infected person. The finding means it is unlikely that an infected animal or environmental conditions, such as the weather, are to blame. Since the beginning of February 2009, when the latest outbreak appeared, 628 people have fallen ill, compared with 482 in all of 2008.

Macquarie University researchers say their testing is experimental, and unlikely to identify the origin of the current outbreak, but they hope their work will lead to the development of an inexpensive automated test to quickly identify parasite strains involved in future outbreaks, allowing sources to be rapidly traced and infections contained.

Michelle Power, of Macquarie's biological sciences department, said cryptosporidium outbreaks were difficult to trace using existing technology. There are two key parasite "species" that infect people: Cryptosporidium hominis, only contracted by direct human to human contact, and Cryptosporidium parvum, which can also be transmitted by animals. For each type there are about 40 different strains.

However, virtually nothing is known about which strains were responsible for most outbreaks. A decade after the contamination of Warragamba Dam, which forced residents of Sydney to boil their water, "we still just know that it was cryptosporidium," Dr Power said. "To put it simply, we're looking for the easiest way to fingerprint the organisms."

With the new test it should be possible to compare results from individual patients to seek common patterns. "We could look to see if they had all eaten at the same restaurant, or been to the same day-care center or swimming pool."

The NSW Health Department has provided hundreds of fecal samples from the latest outbreak for testing by a Macquarie University parasite researcher, Liette Waldron. "We have analysed about 250 samples from the current outbreak, and they are all the same strain" of Cryptosporidium hominis, Dr Power said.

If it had originated from different sources she would have expected to see multiple strains. When sporadic cases were analyzed, they identified 24 strains, involving both the human and animal species. Dr Power also said people who were infected, but did not necessarily appear ill, usually had 5000 to 10,000 parasites per gram of faces. However, some samples from the latest outbreak contained more than 1 million parasites. "The more parasites you see, the more nasty it is."

Over the next two years the project, funded by the Australian Research Council and the Health Department, will "fingerprint" parasites from up to 4000 cryptosporidium patients.
(ProMED 4/1/09)

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Australia (Northern Territory): Man dies of Murray Valley encephalitis
The family of a Northern Territory man who died of Murray Valley encephalitis says they are concerned the public has not been properly warned about the dangers of the mosquito-borne disease. The 58-year-old man died of brain failure, after contracting the disease in Darwin's rural area, where he worked and lived. A member of his family says he was admitted to Royal Darwin Hospital in early March 2009. He died on 20 Mar 2009.

The Health Department did not release a warning about the dangers of Murray Valley encephalitis until the day of the victim's death, and did not announce that he had died until 23 Mar 2009. The family does not want anyone else to go through the grief they have experienced.

The authorities say the chance of contracting Murray Valley encephalitis is small, but they are calling on people to avoid being bitten by mosquitoes.

Dr Jim Burrow, a neurologist at Royal Darwin Hospital, said it was the first such death within the Darwin region in the past 10 years. There is no specific treatment for the virus, which can be lethal in some people, he said. "But even if you do survive, there's a large number of people who have a major disability afterwards. So the only thing that we can do is to avoid getting bitten by the mosquitoes. But having said that, we shouldn't panic because it is a rare condition," he added. He said in the last 30 years there have only been 20 people in the Territory who have contracted the disease. "And of people who we believe are infected by the virus. . .only about one in 500 or one in 1000 will actually develop the disease."
(ProMED 3/25/09)

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Australia (Pilbarra): Bat bite sparks health warning
A Muswellbrook woman is being treated for Australian bat lyssavirus infection after she was attacked by a bat in the courtyard of her Brooke Street home during the week of 11 Mar 2009. The woman will undergo five injections over a 28 day period, the standard treatment for a patient who has been scratched or bitten by a bat.

During the night 11 Mar 2009 when she heard the bark of a dog she was caring for. When she went to investigate, she was shocked to see him barking and jumping at a bat on the ground. When she turned and went to head back up the steps of her patio she felt another bat land on her head. Amid her screams and frantic attempts to get the bat out of her hair, the original bat that had been wrestling with the dog, managed to fly onto her back. She said it seemed like five minutes before she could get the bats off her body. She ran inside and phoned a friend and sought medical attention for the scratches she had received. "I had a big scratch where a claw ripped open my skin on my arm and a puncture mark on my head where one of the bats bit me."

She is now on a campaign to make sure people know of the health risks associated with flying foxes. "I think people need to know that they can carry this deadly virus and if they are bitten or scratched by a bat, they should head straight to their doctor," she said.
(ProMED 3/20/09)

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China (Shandong): Thousands of children ailed by hand-foot-mouth disease
Thousands of children in east and central China have been sickened by hand-foot-mouth disease (HFMD), the government and state press said on 24 Mar 2009. Furthermore, nineteen Chinese children have died so far in 2009, as the disease has spread across the country, the Ministry of Health said on 27 Mar 2009. The ministry recorded 41,846 cases of hand-foot-mouth disease in 30 provinces and regions, excluding Tibet, since the beginning of 2009, ministry spokesman Deng Haihua said.

About 94 percent of the patients were children under 5 years old, 75 percent were affected by the enterovirus 71, and 94 suffered severe symptoms, Deng said. The disease had spread to a wider area, mainly in rural areas, Deng said, adding that a fifth of the cases reported in 2009 were in Henan and Shandong provinces.

Researchers are calling for a better surveillance system to detect the disease and for action to speed up vaccine development. "The situation of preventing and containing hand, foot and mouth disease is very serious at the moment," Deng Haihua, spokesman for China's health ministry, said. More cases are expected, as the disease normally peaks between May and July. In the absence of a drug treatment, the ministry is focusing on prevention and containment.

The outbreak is the latest in a series to have hit China in recent years, caused by a fast-spreading virus called enterovirus 71. "The persistence of enterovirus 71 outbreaks in China is a wake-up call," says Jane Cardosa, a virologist at the University Malaysia Sarawak in Kota Samarahan. In 1997, Sarawak saw the first outbreak of hand, foot and mouth disease in the Asia-Pacific region. The disease causes flu-like symptoms, along with rashes on the hands and feet, and mouth ulcers. It can be caused by many types of human enterovirus belonging to the family Picornaviridae, which are mainly transmitted through fecal or oral routes. Although normally mild, the disease can be life-threatening: some viruses, particularly enterovirus 71, can cause inflammation of the brain stem, resulting in heart failure and fluid accumulation in the lungs.

In 1997 in Sarawak, more than 2600 cases of the disease were reported and 29 people died. The next year in Chinese Taipei, there were 129,000 reported cases and 78 deaths. In mainland China, the first reported case was in Shenzhen, Guangdong province, in 1999. At first, outbreaks were local and there were no reported fatalities. But since 2004, the outbreaks have become more severe and widespread, says Xu Wenbo, an infectious-disease expert at the Beijing-based China Center for Disease Control and Prevention.
(ProMED 3/24/09, 3/27/09, 4/1/09)

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Chinese Taipei: Angiostrongylus in Thai workers after consuming raw snails
Earlier in March 2009, four out of five Thai workers who ate raw snails became infected with the potentially deadly parasite Angiostrongylus, the Department of Health (DOH) said on 25 Mar 2009. Centers for Disease Control Deputy Director Chou Jih-Haw said that three of the workers were in stable condition, while one had left Taiwan and the other had not shown any symptoms of illness.

Three of the workers were reported to have been infected with the parasitic nematode Angiostrongylus cantonensis—an elongated cylindrical worm—early in March 2009 and developed symptoms of eosinophilic meningitis, including headaches, fever and vomiting, Chou said. The DOH discovered that the trio and some of their friends had caught apple snails (Pomacea canaliculata) in fish ponds in southern Taiwan and eaten them raw with sauce.

Snails are usually the primary host of the worm, also known as the rat lungworm, which is a parasite endemic to Southeast Asia and the Pacific region. Humans become infected by ingesting the parasite's larvae, which are then carried in the blood to the central nervous system. This can result in eosinophilic meningitis, which is characterized in the early stages by severe and acute headaches, fever, nausea and vomiting, and stiffness of the neck, and can result in death or permanent brain damage.

Chou said that it was once believed that eating giant African snails could cure certain illnesses and that there were frequent reports in Taiwan of infections of this type of roundworm. A 70-year-old man in Kaohsiung was treated for the same conditions in 2007 after eating raw frogs in an effort to cure back pain. Another case in 2005 saw Hualien's Tzu-Chi Buddhist General Hospital treat a 48-year-old man who had become infected with the parasite after eating raw snails. In 1998, eight Thai workers came down with eosinophilic meningitis as result of eating raw snails and in 1999, Kaohsiung Veterans General Hospital reported that nine Thai laborers had been infected with rat lungworms.
(ProMED 3/27/09)

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Indonesia: 200 residents diagnosed with chikungunya virus
The local health agency in Banyumas regency has diagnosed around 200 residents from villages in three districts as being infected with the mosquito-borne chikungunya virus (CHIKV). Around 100 of the patients were from Sumpiuh district, and the rest from Somagede and Kemranjen districts, all bordering each other. Banyumas Health Agency head Gempol Suwandono told reporters on 18 Mar 2009 that the three districts were vulnerable to the disease.

"We received reports from each community health center in the three districts" he said. He added that the three districts were labeled as vulnerable areas a few years ago. "Three years ago, we determined they were safe, but now the disease has recurred," Gempol said, adding that many swampy areas and stagnant pools were found in the districts, thus providing good breeding grounds for mosquitoes. "I have urged residents to maintain cleanliness and not leave stagnant water lying around."
(ProMED 3/26/09)

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Indonesia (Bali): Two more fatalities in rabies outbreak
Rabies in Bali has claimed two more victims. A 46-year-old patient died at Sanglah General Hospital on 23 Mar 2009 after being hospitalized for one day. The second victim, a 46-year-old woman was admitted to the same hospital in the early hours of 26 Mar 2009 and died 17 hours later.

The first patient, a resident of Jalan Uluwatu on the Ungasan peninsula in south Bali, was confirmed by hospital officials as clinically positive for the deadly disease, when initially presenting at the hospital with a throat infection, fits of anger, and phobias of water and wind. According to Radar Bali, the patient succumbed to rabies three months after being bitten by a stray dog, despite receiving an anti-rabies shot. Doctors blame the patient's failure to undergo the complete three-shot therapy protocol.

The 46-year-old woman was admitted to hospital after developing a phobia of water. She was reportedly bitten by both a stray dog and a pet dog five months ago, but due to a fear of needles refused the recommended series of three shots.

These patients' deaths are counted as the 8th and 9th fatalities traced to the current outbreak of rabies on the island of Bali. The previous seven victims also died after being bitten by dogs. There have been proposals expressed, during various discussions on how to handle rabies in Bali, that dog owners should be punished if their dogs bite people. The aim is to involve the public in preventing the spread of rabies.
(ProMED 3/26/09, ProMED 3/31/09)

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Americas
USA: FDA approves new vaccine to prevent Japanese encephalitis
The U.S. Food and Drug Administration (FDA) on 30 Mar 2009 approved IXIARO, a vaccine to prevent Japanese encephalitis (JE), which is caused by a mosquito-transmitted virus found mainly in Asia. IXIARO will be the only vaccine for JE available in the United States. "This vaccine offers protection for individuals who travel to or live in areas where outbreaks are known to occur," said Karen Midthun, M.D., acting director of the FDA's Center for Biologics Evaluation and Research. In Asia, JE affects about 30,000 to 50,000 people each year, resulting in 10 000 to 15 000 deaths. JE is rarely seen in the United States, with very few cases reported among civilians and military who have been to Asia.

The virus that causes JE affects membranes around the brain, and mild infections can occur without apparent symptoms other than fever and headache. In people who develop severe disease, JE usually starts as a flu-like illness but can worsen, causing high fever, neck stiffness, brain damage, coma, or even death. The disease is transmitted from wild birds and pigs via infected mosquitoes; it is not spread from human to human.
(ProMED 4/1/09)

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USA (Arizona): State veterinarian urges precautions due to large rabies outbreak
The state of Arizona is being hit with the biggest outbreak of rabies that it has seen in a while, according to state veterinarian Elisabeth Lawaczeck. So far in 2009 there have been 62 animals confirmed infected with rabies, according to Lawaczeck.

A 21-year-old Phoenix resident was bitten by a rabid bat at a family get-together in Northern Arizona. "Something flew at me, I didn't know what it was," she said. "I remember fumbling with it a lot. It was really furry. It bit me and it flew away." The woman was taken to the emergency room where she was treated for rabies. She had to undergo a series of painful shots that lasted six months.

With the current outbreak of rabies, Lawaczeck says people should take precautions when they go hiking or camping. "When you're camping you want to make sure you are sleeping inside a tent and not just on the ground or on a tarp. When you're hiking on the trails you should take a hiking stick if you are in an area where there is reported rabies in the past," Lawaczeck said.

Lawaczeck also said most rabies cases occur in skunks and foxes in Southern Arizona but there have been recent outbreaks in the Flagstaff area as well.
(ProMED 3/27/09)

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USA (Hawaii): Two rat lungworm patients recovering
Two Big Island victims of a rare disease spread through homegrown vegetables have emerged from their comas. The 38-year-old woman has come out of the coma caused by rat lungworm disease enough to respond to friends and her parents. She has been hospitalized since 8 Dec 2008. The 24-year-old man is now conscious and able to track people with his eyes. He was put in intensive care in January 2009.

Both remain at Hilo Medical Center, where they are breathing with the assistance of a machine. The disease is spread through vegetables containing larvae of a slug that carries the rat lungworm. A third person who contracted rat lungworm disease has recovered enough to walk and live at home.
(ProMED 3/26/09)

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USA (Tennessee): Ten colonoscopy patients diagnosed with hepatitis
Equipment used on more than 10,000 thousand patients at three facilities wasn't properly sterilized. The Veterans Affairs (VA) department says 10 people have tested positive for infectious liver disease since they were exposed to contaminated colonoscopy equipment. The 10 are among thousands of patients who have been warned to get blood tests since being treated at VA facilities in Murfreesboro, Tennessee, Miami, Florida and Augusta, Georgia. All three sites failed to properly sterilize equipment between treatments.

VA spokeswoman Katie Roberts said 27 Mar 2009 that four Tennessee patients have tested positive for hepatitis B. A total of six have tested positive for hepatitis C, a potentially life-threatening form of the viral infection that can cause permanent liver damage.

The 10 identified hepatitis patients seem to have contracted infection during examination by colonoscopy at the VA hospital in Tennessee. Inadequate sterilization of equipment seems to have occurred at the other two hospitals, although cases of hepatitis have not yet been reported. Blood-borne transmission of infection should not be an accompaniment of any hospital procedure. The precise number of patients exposed at each hospital has not been disclosed.
(ProMED 3/28/09)

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3. 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.
- 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 their new report: Pandemic Influenza, Electricity, and the Coal Supply Chain.
- 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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DENGUE
Viet Nam
More than 2200 people have been affected by dengue fever in Ho Chi Minh City since early 2009, an increase of 8 percent over the same period in 2008. The Municipal Health Department reports that as many as 90 percent of households in such districts as Binh Thanh, 12, and 6 were found to have mosquitoes.

The Preventive Medicine Department under the Health Ministry held a meeting on 27 Mar 2009 to launch a national project to prevent a possible dengue fever epidemic, especially in southern provinces during the monsoon season.

The project, worth more than VND 91 billion [USD 5.1 million] is expected to reduce the infection and fatality rates by 10 percent from the average level of the 2003-2007 period.
(ProMED 3/31/09)

Indonesia
The West Java administration has declared all its municipalities and regencies under threat from dengue fever after local authorities recorded more than 6000 cases of the disease, 47 of them fatal, as of March 2009.

Wahyu Saputra, head of the provincial health agency's disease control section, stated on 20 Mar 2009 that of the affected areas, Depok had recorded the most cases with 637, followed by Sumedang, Garut, Subang and Purwakarta districts with more than 300 infections each.

But he added the figures were slightly down from those in the same period of 2008, when more than 6800 cases were recorded, 65 of them fatal. "To prevent the figures from rising, we are focusing on campaigning for a healthy environment. We're also providing information on symptoms of the mosquito-borne disease to prevent more fatalities," Wahyu said.
(ProMED 3/31/09)

Australia
An end to Australia's worst dengue fever outbreak may be in sight, as the rate of infection slows in far north Queensland. The number of infections has slowed to fewer than 10 a day, down from a peak of about 20 a day in the Cairns area, the epicenter of the outbreak.

However, health authorities have warned residents throughout the north to remain on guard, because fresh rainfall and complacency could see the epidemic spiral out of control. "We've had some encouraging signs in the last few weeks that the number of cases has declined, (but) we've still got a long way to go even if that is sustained," Queensland Health Physician Dr Frank Beard said. "We're still getting a significant number of cases, and it's likely to be several months before we can be confident of getting rid of it."

Authorities are hoping the onset of the dry season in the coming months will give them a better opportunity to cull the population of the Aedes aegypti mosquito, which spreads the disease. If the disease is not eradicated during the dry months, there is a significant risk it could become endemic to the region.

So far, 860 people have contracted dengue fever, with the vast majority of cases occurring in the Cairns area. Townsville has also been affected but to a much lesser degree.
(ProMED 3/31/09)

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4. Articles
Influenza Virus Resistance to Antiviral Agents: A Plea for Rational Use
Poland GA et al. Clinic Infect Dis. 26 March 2009. Available at http://www.journals.uchicago.edu/doi/abs/10.1086/598989.

Although influenza vaccine can prevent influenza virus infection, the only therapeutic options to treat influenza virus infection are antiviral agents. At the current time, nearly all influenza A/H3N2 viruses and a percentage of influenza A/H1N1 viruses are adamantane resistant, which leaves only neuraminidase inhibitors available for treatment of infection with these viruses. In December 2008, the Centers for Disease Control and Prevention released new data demonstrating that a high percentage of circulating influenza A/H1N1 viruses are now resistant to oseltamivir. In addition, oseltamivir‐resistant influenza B and A/H5N1 viruses have been identified. Thus, use of monotherapy for influenza virus infection is irrational and may contribute to mutational pressure for further selection of antiviral‐resistant strains. History has demonstrated that monotherapy for influenza virus infection leads to resistance, resulting in the use of a new monotherapy agent followed by resistance to that new agent and thus resulting in a background of viruses resistant to both drugs. We argue that combination antiviral therapy, new guidelines for indications for treatment, point‐of‐care diagnostic testing, and a universal influenza vaccination recommendation are critical to protecting the population against influenza virus and to preserving the benefits of antiviral agents.

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DNA vaccination protects against an influenza challenge in a double-blind randomised placebo-controlled phase 1b clinical trial
Jones S et al. Vaccine. 21 April 2009; 27(18): 2506-2512.

Abstract
Background. We have developed a Trivalent DNA vaccine for influenza consisting of three plasmids expressing haemagglutinin from different seasonal influenza virus strains delivered using PMED™ (particle mediated epidermal delivery). We set out to determine whether this vaccine (with and without a molecular adjuvant DNA Encoded Immunostimulator-Labile Toxin (DEI-LT)) could protect subjects from a controlled influenza virus challenge.

Methods. Healthy adult subjects were screened for susceptibility to infection with influenza A/H3 Panama/2007/99 then vaccinated with 4 μg Trivalent influenza DNA vaccine, 2 μg Trivalent influenza DNA vaccine plus DEI-LT or placebo. Safety and serological responses to vaccination were assessed and on Day 56 subjects were challenged with A/H3 Panama/2007/99 virus.

Results. Vaccination with 4 μg Trivalent or 2 μg Trivalent/DEI-LT was well tolerated and induced antibody responses to two of the three influenza virus vaccine strains. Post challenge, subjects in the 4 μg Trivalent group (N = 27) showed reductions in disease symptoms and viral shedding compared to placebo (N = 27), with an overall vaccine efficacy of 41% (95% confidence interval (CI) = −1.5, 67.7) for ‘Any illness with or without fever’ and 53% for ‘Upper respiratory tract infection’ (95% CI = 8.0, 77.7).

Conclusion. It was concluded that PMED vaccination with 4 μg Trivalent influenza DNA vaccine was safe and elicited immunological responses that protected human subjects from influenza; this is the first report of protection of human subjects from disease by DNA vaccination.

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Avian influenza virus (H5N1): effects of physico-chemical factors on its survival
Shahid MA et al. Virology Journal. 28 Mar 2009; 38(6). Available at http://www.virologyj.com/content/6/1/38.

Abstract (Provisional)
Present study was performed to determine the effects of physical and chemical agents on infective potential of highly pathogenic avian influenza (HPAI) H5N1 (local strain) virus recently isolated in Pakistan during 2006 outbreak. H5N1 virus having titer 108.3 ELD50 /ml was mixed with sterilized peptone water to get final dilution of 4HA units and then exposed to physical (temperature, pH and ultraviolet light) and chemical (formalin, phenol crystals, iodine crystals, CID 20, virkon(R)-S, zeptin 10%, KEPCIDE 300, KEPCIDE 400, lifebuoy, surf excel and caustic soda) agents. Harvested amnio-allantoic fluid (AAF) from embryonated chicken eggs inoculated with H5N1 treated virus (0.2 ml/egg) was subjected to haemagglutination (HA) and haemagglutination inhibition (HI) tests. H5N1 virus lost infectivity after 30 min at 56degreesC, after 1 day at 28degreesC but remained viable for more than 100 days at 4degreesC. Acidic pH (1, 3) and basic pH (11, 13) were virucidal after 6 h contact time; however virus retained infectivity at pH 5 (18 h), 7 and 9 (more than 24 h). UV light was proved ineffectual in inactivating virus completely even after 60 min. Soap (lifebuoy(R)), detergent (surf excel(R)) and alkali (caustic soda) destroyed infectivity after 5 min at 0.1, 0.2 and 0.3% dilution. All commercially available disinfectants inactivated virus at recommended concentrations. Results of present study would be helpful in implementing bio-security measures at farms/ hatcheries levels in the wake of avian influenza virus (AIV) outbreak.

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A comparison of the pathogenicity of avian and swine H5N1 influenza viruses in Indonesia
Takano R et al. Arch of Virology. 14 March 2009. Available at http://www.springerlink.com/content/x28968q677027254/?p=63832bf7dd6f48b59a02cfeb644f01ea&pi=14.

Abstract
Highly pathogenic avian influenza H5N1 viruses are circulating in many countries. We recently discovered that these viruses have been transmitted to pigs on multiple occasions in Indonesia. To investigate whether avian H5N1 influenza viruses adapted to mammals through their introduction into pigs, we examined the growth of avian and swine isolates in cell culture and compared their pathogenicity in mice. We found that swine isolates were less virulent to mice than avian isolates, suggesting that the viruses became attenuated during their replication in pigs. Continuous surveillance of H5N1 viruses among pigs is clearly warranted.

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Estimation of Influenza Vaccine Effectiveness from Routine Surveillance Data
Kelly H et al. PLoS One. 31 Mar 2009; 4(3). Available at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0005079.

Abstract

Background. Influenza vaccines are reviewed each year, and often changed, in an effort to maintain their effectiveness against drifted influenza viruses. There is however no regular review of influenza vaccine effectiveness during, or at the end of, Australian influenza seasons. It is possible to use a case control method to estimate vaccine effectiveness from surveillance data when all patients in a surveillance system are tested for influenza and their vaccination status is known.

Methodology/Principal Findings. Influenza-like illness (ILI) surveillance is conducted during the influenza season in sentinel general practices scattered throughout Victoria, Australia. Over five seasons 2003–7, data on age, sex and vaccination status were collected and nose and throat swabs were offered to patients presenting within three days of the onset of their symptoms. Swabs were tested using a reverse transcriptase polymerase chain reaction (RT-PCR) test. Those positive for influenza were sent to the World Health Organization (WHO) Collaborating Centre for Reference and Research on Influenza where influenza virus culture and strain identification was attempted. We used a retrospective case control design in five consecutive influenza seasons, and estimated influenza vaccine effectiveness (VE) for patients of all ages to be 53% (95% CI 38–64), but 41% (95% CI 19–57) adjusted for age group and year. The adjusted VE for all adults aged at least 20 years, the age groups for whom a benefit of vaccination could be shown, was 51% (95% CI 34–63). Comparison of VE estimates with vaccine and circulating strain matches across the years did not reveal any significant differences.

Conclusions/Significance. These estimates support other field studies of influenza vaccine effectiveness, given that theoretical considerations suggest that these values may underestimate true effectiveness, depending on test specificity and the ratio of the influenza ILI attack rate to the non-influenza ILI attack rate. Incomplete recording of vaccination status and under-representation of children in patients from whom a swab was collected limit the data. Improvements have been implemented for prospective studies.

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Use of Unstructured Event-Based Reports for Global Infectious Disease Surveillance
Keller M et al. Emerg Infect Dis. 2009 May. Available at http://www.cdc.gov/eid/content/15/5/pdfs/08-1114.pdf.

Free or low-cost sources of unstructured information, such as Internet news and online discussion sites, provide detailed local and near real-time data on disease outbreaks, even in countries that lack traditional public health surveillance. To improve public health surveillance and, ultimately, interventions, we examined 3 primary systems that process event-based outbreak information: Global Public Health Intelligence Network, HealthMap, and EpiSPIDER. Despite similarities among them, these systems are highly complementary because they monitor different data types, rely on varying levels of automation and human analysis, and distribute distinct information. Future development should focus on linking these systems more closely to public health practitioners in the field and establishing collaborative networks for alert verification and dissemination. Such development would further establish event-based monitoring as an invaluable public health resource that provides critical context and an alternative to traditional indicator-based outbreak reporting.

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Conventional and future diagnostics for avian influenza
Charlton B et al. Comp Immunol Microbiol Infect Dis. July 2009; 32(4): 341-350.

Abstract
The significant and continued transboundary spread of Asian avian influenza H5N1 since 2003, paired with documented transmission from avian species to humans and other mammals, has focused global attention on avian influenza virus detection and diagnostic strategies. While the historic and conventional laboratory methods used for isolation and identification of the virus and for detection of specific antibodies continued to be widely applied, new and emerging technologies are rapidly being adapted to support avian influenza virus surveillance and diagnosis worldwide. Molecular tools in particular are advancing toward lab-on-chip and fully integrated technologies that are capable of same day detection, pathotyping, and phylogenetic characterization of influenza A viruses obtained from clinical specimens. The future of avian influenza diagnostics, rather than moving toward a single approach, is wisely adopting a strategy that takes advantage of the range of conventional and advancing technologies to be used in “fit-for-purpose” testing.

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Highly pathogenic H5N1 avian influenza virus: Cause of the next pandemic?
Pappaioanou M. Comp Immunol Microbiol Infect Dis. July 2009; 32(4): 287-300.

Abstract
Since 1997, when human infections with a highly pathogenic (HP) avian influenza A virus (AIV) subtype H5N1 – previously infecting only birds – were identified in a Hong Kong outbreak, global attention has focused on the potential for this virus to cause the next pandemic. From December 2003, an unprecedented H5N1 epizootic in poultry and migrating wild birds has spread across Asia and into Europe, the Middle East, and Africa. Humans in close contact with sick poultry and on rare occasion with other infected humans, have become infected. As of early March 2007, 12 countries have reported 167 deaths among 277 laboratory-confirmed human infections to WHO. WHO has declared the world to be in Phase 3 of a Pandemic Alert Period. This paper reviews the evolution of HP AIV H5N1, molecular changes that enable AIVs to infect and replicate in human cells and spread efficiently from person-to-person, and strategies to prevent the emergence of a pandemic virus.

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5. Notifications
APEC Conference for the Surveillance, Treatment, Laboratory Diagnosis and Vaccine Development of Enteroviruses
Location: Chinese Taipei; Date : May 14-15, 2009

Chinese Taipei would like to invite all APEC members to participant in this conference which will be held in Taipei on May 14-15, 2009. The deadline for the registration is 10 April 2009. For the further information, please contact with Conference Secretariat Ms Ying- Chen Cheng (Amelia) by e-mail at amelia@mpat.org.tw or by telephone at 886-2-2321-2362 ext 20.

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Health Sciences Online has launched
Health Sciences Online is the only authoritative, comprehensive, free, and ad-free resource spanning across the health sciences. Health professionals in training and in practice can search over 50,000 courses, references, guidelines, and other high-quality, current, free, and ad-free health sciences resources. It contains text searching and reading capabilities in 42 languages.

Founding collaborators for this site include the US CDC, World Bank, the American College of Preventive Medicine, and the University of British Columbia. Funders include WHO, the Canadian government, the NATO Science for Peace initiative, and the Annenberg Physician Training Program.

The site can be accessed at www.hso.info.

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APEC EINet director to attend WHO meeting on outbreak response coordination
APEC EINet's Dr. Ann Marie Kimball will be attending WHO's Global Outbreak Alert and Response Network (GOARN) Meeting of Partner's in Geneva, Switzerland 16 and 17 April 2009. GOARN has been a framework to strengthen operational coordination, build response capacity and provide technical support for international outbreak response to over 110 major outbreaks. The objective of this meeting is to examine the impact on GOARN of recent developments, including the IHR (2005), advances in global and regional health security issues and concerns about priority diseases, including pandemic influenza, yellow fever, VHFs, zoonoses, and others. The meeting will bring together GOARN partners to look at both technical and operational functions of the Network and Steering Committee, and suggest realistic and sustainable work plan for the strategic development of technical collaborations and networking among GOARN partners.

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Introducing the Journal of Bacteriology Research
Call for papers: The Journal of Bacteriology Research (JBR) is a multidisciplinary peer-reviewed journal that will be published monthly by Academic Journals beginning April 2009. JBR is dedicated to increasing the depth of the subject across disciplines with the ultimate aim of expanding knowledge of the subject. JBR will cover all areas of the subject. The journal welcomes the submission of manuscripts that meet the general criteria of significance and scientific excellence, and will publish:
- Original articles in basic and applied research
- Case studies
- Critical reviews, surveys, opinions, commentaries and essays

Additional information available at http://www.academicjournals.org/JBR/Instruction.htm.

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Researchers launch online vector database
To ease the development of risk maps and other assessments, an international group of researchers has developed a Web-based, publicly accessible Disease Vector Database. The purpose is to gather and display data on the geographic distribution of infectious disease vectors and reservoirs, according to a report in the March issue of PLoS Neglected Tropical Diseases. The database, housed at the University of Texas at Austin, currently contains records for dengue and malaria vectors, as well as Chagas disease and leishmaniasis vectors and reservoirs.

Access the database at http://www.consnet.org/DiseaseVectorsDatabase/.

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CDC Symposium on Drug-resistant and Vaccine-escape HBV Mutants
Location: Atlanta, Georgia, USA
Venue: CDC Roybal Campus
Dates: 4-5 Jun 2009
Registration is free

Program and online registration details available at http://www.cdc.gov/hepatitis/hbvsymposium2009.

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 apecein@u.washington.edu