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Vol. Vol. XI No. 10 ~EINet News Brief ~ 16 May 2008 ~ EINet News Briefs ~ May 16, 2008


*****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
- Global: Cumulative number of human cases of avian influenza A/(H5N1)
- India (Darjeeling): Officials frustrated over slow culling operations in Northeastern India
- Indonesia (Jakarta): Two siblings die of suspected H5N1 avian influenza infection
- Viet Nam (Can Tho City): H5N1 avian influenza resurfaces in poultry flocks
- South Korea (Seoul): Officials claim to have culled all poultry in the capital city

2. Infectious Disease News
- Russia (Stavropol): Officials declare Crimean-Congo hemorrhagic fever situation “serious”
- Russia: Officials report two cases of botulism infection during the first quarter of 2008
- Singapore: Officials report an imported case of chikungunya
- Peru: Epidemiology officials confirm three cases of cutaneous anthrax
- Peru: Two more probable yellow fever cases
- Peru: Officials confident in control of imported measles case
- Peru: Toxins suspected in death of two sailors, quarantine lifted
- USA (South Carolina): 33 people possibly exposed to rabid baby raccoon
- USA (Colorado): Kiowa county man dies from hantavirus infection
- USA (New York): Health officials attempt to raise awareness of shigellosis
- USA (Washington): Measles outbreak continues in Grant County, possible exposure in King County
- Canada: Health authorities worry as measles outbreak continues

3. Updates
- AVIAN/PANDEMIC INFLUENZA
- Hand, foot and mouth disease – *Major International Outbreak*
- DENGUE

4. Articles
- Enterovirus Déjà Vu
- An eight-year study of epidemiologic features of enterovirus 71 infection in Taiwan
- Salmonellosis Outcomes Differ Substantially by Serotype
- Crystal structures of oseltamivir-resistant influenza virus neuraminidase
- Cross-Recognition of Avian H5N1 Influenza Virus by Human Cytotoxic T-Lymphocyte
- Multi-antigen vaccines based on complex adenovirus vectors induce protective

5. Notifications
- APEC EINet Pandemic Influenza Preparedness Virtual
- Critical care panel tackles disaster preparation, surge capacity, rationing
- Proposed Guidance on Workplace Stockpiling of Respirators and Facemasks
- CDC guide to hand, foot, and mouth disease


1. Influenza News

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

2008
China / 3 (3)
Egypt / 7 (3)
Indonesia / 16 (13)
Viet Nam / 5 (5)
Total / 31 (24)

2007
Cambodia / 1 (1)
China / 5 (3)
Egypt / 25 (9)
Indonesia / 42 (37)
Laos / 2 (2)
Myanmar / 1 (0)
Nigeria / 1 (1)
Pakistan / 3 (1)
Viet Nam 8 (5)
Total / 88 (59)

2006
Azerbaijan / 8 (5)
Cambodia / 2 (2)
China / 13 (8)
Djibouti / 1 (0)
Egypt / 18 (10)
Indonesia / 55(45)
Iraq / 3 (2)
Thailand / 3 (3)
Turkey / 12 (4)
Total / 115 (79)

2005
Cambodia / 4 (4)
China / 8 (5)
Indonesia / 20 (13)
Thailand / 5 (2) Viet Nam / 61 (19)
Total / 98 (43)

2004
Thailand / 17 (12)
Viet Nam / 29 (20)
Total / 46 (32)

2003
China / 1 (1)
Viet Nam / 3 (3)
Total / 4 (4)


Total no. confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 382(241).
(WHO 4.30.08 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 4.17.08)


WHO's maps showing world's areas affected by H5N1 avian influenza (last updated 5.6.08): http://gamapserver.who.int/mapLibrary/


WHO’s timeline of important H5N1-related events (last updated 5.2.08): http://www.who.int/csr/disease/avian_influenza/ai_timeline/en/index.html

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Asia
India (Darjeeling): Officials frustrated over slow culling operations in Northeastern India
Amidst a slow culling operation in avian flu-affected Darjeeling district due to noncooperation by owners of fowl, a fresh report of bird deaths worsened the situation. District magistrate Rajesh Pandey on 12 May 2008 said that the deadline was extended, as only 9,500 birds were culled against the target of culling 18,000 birds by 11 May 2008. Animal Resources Development department sources said that the progress of culling was not as expected because of noncooperation by poultry owners in some areas. The target was increased to 20,000 and was expected to be completed by 13 May 2008. To encourage poultry owners, the department announced revised compensation for birds culled: Rs 75 (USD 1.77) for a duck, Rs 50 (USD 1.18) for a layer, Rs 40 (USD 0.94) for a broiler, Rs 35 (USD 0.83) for a duckling, Rs 20 (USD 0.47]) for a chick and Rs 2 (USD 0.05) for an egg.

The situation, however, turned worse following reports of the deaths of a crow, two swallows and seven fowl from Bijanbari area in Darjeeling on 11 May 2008. Unofficial reports, however, claimed the deaths of 100 birds. The outbreak of avian influenza at Bagdogra, Matigara, Naxalbari in Siliguri and Sukna in Kurseong sub-division was confirmed by High Security Animal Disease Laboratory, Bhopal. The administration has banned trading on chicken and poultry products in the affected areas. Meanwhile, there were allegations that the administration, under pressure from the business community, was not banning the sale of poultry products in this commercial hub. The relaxation could cause problems, as there was every possibility that a supply of chickens and poultry products could come from the affected areas, which were within 15 km of this town.
(ProMED 5.14.08)

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Indonesia (Jakarta): Two siblings die of suspected H5N1 avian influenza infection
Two teenagers from the same family have died within 10 days because of suspected bird flu in Jakarta, prompting health officials to take blood test of the other members of the family, local press said on 14 May 2008.

A 16-year-old girl died four days after being admitted to the Persahabatan Hospital in the Indonesian capital on 8 May 2008 with laboratory test later confirming she had the avian flu virus. She had been treated at the isolated room exclusively for bird flu patients but doctors failed to save her life. Ten days before her death, her 15-year-old brother died after a brief treatment at another hospital with symptoms similar to bird flu.

“The symptoms were just the same: high fever, cough and faint. We thought it was the common (seasonal) flu so he didn't stay at the hospital, but then he died,” the father of the ill-fated teenagers, said. But it cannot be confirmed that bird flu had caused the boy's death as he didn't take a blood test. The family lives in a densely populated neighborhood where a nearby house rears chickens.

Apart from the two cases, Indonesia has so far confirmed 133 bird flu cases in human with 107 deaths since the virus was first reported in 2003.
(ProMED 5.14.08)

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Viet Nam (Can Tho City): H5N1 avian influenza resurfaces in poultry flocks
Bird flu has stricken fowl flocks in Viet Nam's southern Can Tho City, raising the total number of affected localities in the country to three, according to Viet Nam's Department of Animal Health on 8 May 2008. The bird flu outbreak killed 1,131 poultry, including 1,070 chickens raised by a household in the city's Phong Dien rural district. Local veterinary forces on 7 May 2008 culled the remainders of 829 healthy fowls in the affected flocks to prevent the disease's spread. Viet Nam currently has three localities having poultry being hit by bird flu: northern Son La province, southern Vinh Long province and southern Can Tho city, the department said.
(ProMED 5.10.08)

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South Korea (Seoul): Officials claim to have culled all poultry in the capital city
South Korean officials said on 12 May 2008 that they have killed all poultry in Seoul, the capital, to curb the spread of bird flu following a new outbreak of the disease in the city. Quarantine officials destroyed 15,000 chickens, ducks, pheasants, and turkeys raised in farms, restaurants, schools, and homes in the capital, said Kim Yoon-kyu, a Seoul Metropolitan Government official. The Seoul government said the slaughter was necessary to contain the disease. It said now it will focus on preventing live poultry from being brought into the capital.

The slaughter began on 11 May 2008, hours after authorities confirmed Seoul's second outbreak of bird flu in less than a week. The slaughter did not affect parrots, parakeets, and canaries because they have little chance of spreading the disease, Kim said. On 12 May 2008, government tests confirmed the H5N1 viruscaused the latest outbreak in Seoul, said Yoon Young-ku, a spokesman at the Agriculture Ministry. The tests also confirmed two additional outbreaks of the virus in Busan, bringing to 31 the total number of outbreaks in South Korea, he said. Bird flu began sweeping southern parts of the country in April 2008 for the first time in more than a year, forcing the slaughter of about 6.8 million birds.
(ProMED 5.14.08)

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2. Infectious Disease News

Europe/Near East
Russia (Stavropol): Officials declare Crimean-Congo hemorrhagic fever situation “serious”
The administration of Rospotrebnadzor (Federal Trade and Public Health Inspection Authority) for Stavropol Krai considers that the Crimean-Congo hemorrhagic fever (CCHF) situation in the region is serious. One patient died on 13 May 2008. The agency reports that so far there are nine other patients with CCHF registered in 2008. These patients are from eight regions of the Stavropol Krai. Only three patients were registered during the same period in 2007.
(ProMED 5.15.08)

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Russia: Officials report two cases of botulism infection during the first quarter of 2008
Two cases of botulism were reported during the first quarter of 2008. All the cases were due to consumption of homemade mushrooms or fish. Five cases of botulism with seven affected people have been registered during 2007. For four of the cases, the source of infection was homemade canned fish and for three homemade dried fish.
(ProMED 5.8.08)

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Asia
Singapore: Officials report an imported case of chikungunya
Singapore's Health Ministry confirmed the 17th case of the mosquito-borne chikungunya disease here on 8 May 2008. The ministry revealed that the latest victim was a man that caught the disease overseas recently. He believed he caught the virus while playing golf at Jakarta's Jagorawi Golf and Economy Club a month ago. Since the first locally transmitted case was detected on 14 Jan 2008, so far 13 people have been infected locally, while another four caught the virus overseas, the ministry said. Its spokesman said: “The virus can be carried into Singapore, and the presence of the Aedes mosquito means the threat will remain.”

Like the dengue virus, the chikungunya virus is spread by the Aedes mosquito. Currently, there is no vaccine to prevent chikungunya fever, which is characterized by fever, joint pains, chills and nausea. The ministry said the best way to prevent chikungunya fever is to take precautionary measures to prevent mosquito breeding around the house and to protect oneself against mosquito bites.
(ProMED 5.8.08)

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Americas
Peru: Epidemiology officials confirm three cases of cutaneous anthrax
On 23 Apr 2008 the Lima District Health Unit (DIRESA) notified the General Directorate for Epidemiology of three confirmed cases of cutaneous anthrax from the Caudevilla locality, Supe District.

Case 1: 29-year-old, male worker in the Supe slaughterhouse, who went to the hospital on 16 Apr 2008, presented with an ulceronecrotic skin lesion in the right forearm, with perilesional edema, accompanying fever, and with a Gram-positive smear of the lesion compatible with Bacillus anthracis.

Case 2: 26-year-old female who went to the same hospital on 19 Apr 2008 with a ulceronecrotic skin lesion on the second finger of the left hand, and a Gram-positive swab of the lesion compatible with B. anthracis. On 10 Apr 2008 both patients had participated in a clandestine butchering of a bovine (animal) in Caudevilla, Supe district.

Case 3: 9-year-old female with an ulceronecrotic skin lesion on the dorsum of the right hand and beginning of illness on 21 Apr 2008. This girl participated in washing the viscera of the same animal as in the cases above.
ProMED 5.8.08)

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Peru: Two more probable yellow fever cases
During epidemiological week (EW)17 2008 (20-26 Apr 2008), two probable cases of sylvan (jungle) yellow fever were reported in Peru. The first case was a 23-year-old unvaccinated man from Loreto; the probable location of infection is under investigation. The second case is a 21-year-old man of unknown vaccination status from San Martin. He became ill during EW 15 (6-12 Apr 2008).

During EW 1-17 of 2008, there were 13 reported cases in Peru, including three confirmed cases, six probable cases, and four discarded cases. All of the confirmed cases died.
(ProMED 5.6.08)

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Peru: Officials confident in control of imported measles case
On 1 May 2008, Vesalio Clinic (a private clinic) in San Borja District in Lima reported a probable case of measles. The International Maritime Sanitation, the Callao (main Peruvian port) Epidemiology Office and the General Direction of Epidemiology started an epidemiological investigation into the situation.

The case is a 19-year-old male patient coming from India who departed on 19 Apr 2008 from Bombay heading to Guayaquil, with stops in London and Miami. On 21 Apr 2008, he arrived in Guayaquil and the same day went to Puerto Bolivar, where he boarded a tanker, Berge Nantong. The vessel set sail to Callao on 28 Apr 2008 and arrived there on 30 Apr 2008. Symptoms began on 28 Apr 2008 with malaise, cough, and sore throat. On 30 Apr 2008, he became febrile, with a rash on 1 May 2008, so it was decided to send the patient to a private clinic in Lima (Vesalio clinic), where it was determined that it was a probable case of measles, and they notified the case to the General Direction of Epidemiology. The patient did not leave the ship from 21 Apr to 1 May 2008, when he was taken to Vesalio clinic. On 2 May 2008, the Peruvian National Institute of Health reported the results of ELISA tests, positive IgM and negative IgG for measles in serum. When the case was confirmed, a multidisciplinary team was brought together in order to assess and control the risk for measles transmission from this imported case already identified. After the patient was notified as a probable case of measles, he was isolated for one week. International Maritime Sanitation stated on 1 May 2008 that the crew and every person on the ship had to stay in quarantine while investigations were carried out to determine their immune status for measles and their risk is assessed as a preventive measure against possible transmission of measles through contact.

Two places were identified in which the patient had contact with different persons whose immune status for measles was not initially known: Berge Nantong vessel and Vesalio Clinic, where the patient was initially seen. Thirty-eight contacts were identified in the vessel, including the crew members and persons who boarded the ship after she arrived to Callao. One hundred ninety one persons were identified and vaccinated in Vesalio clinic, including health care personnel who took care of the patient and other patients who were in the clinic while the measles case was hospitalized there.

On 2 May 2008, a clinical examination of all crew of Berge Nantong ship was performed. No febrile cases were found; nobody with a rash was found, so everybody was considered to be in an apparent good health condition. On 2 May 2008, blood samples were taken from 24 persons in the ship (20 crew members and four Peruvian citizens who boarded the ship). The samples were processed by the Peruvian National Institute of Health, and all of them were negative for measles IgM and positive for IgG, so it was interpreted that this population is immune for measles and that the quarantine period should be terminated.
(ProMED 5.5.08)

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Peru: Toxins suspected in death of two sailors, quarantine lifted
Members of the Chang An 168's crew and the Peruvian personnel in contact with them are in good health, and local health authorities therefore lifted the quarantine on 22 Apr 2008. According to the ship's captain, the only symptom in the two fatal cases on board of the ship was fever, five and two hours (respectively) prior to death, but the language barrier has precluded a more detailed investigation. Immunofluorescence showed evidence of adenovirus infection in the two cases and in six other crewmembers. No evidence of other respiratory viruses has been found. Cultures for adenovirus are being processed at this time, but there is still no evidence of a mutant strain. Tests for leptospirosis were negative in all crewmembers. Upon contact with Peruvian health personnel, 15 of the fishermen had mild respiratory symptoms, but none had fever. No evidence of adenovirus or respiratory symptoms has been found on a crewmember that provided mouth-to-mouth breathing to one of the victims. Autopsies on the fatal cases showed evidence of pneumonia and cerebral edema. Histopathology revealed evidence of a toxic process, although samples from the corpses were negative to 12 toxins evaluated. The ship sailed from Yan Tai on 19 Aug 2007 and has remained at sea since. The Chang An 168 remained quarantined since 15 Mar 2008, when it delivered its cargo to the (mother ship) Dong Fen in international waters.
(ProMED 5.5.08)

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USA (South Carolina): 33 people possibly exposed to rabid baby raccoon
The number of people possibly exposed to a rabid raccoon has more than doubled from the number originally reported state officials said on 13 May 2008. The South Carolina Department of Health and Environmental Control (DHEC) also revealed that Okatie residents visiting Wexford Plantation on Hilton Head Island originally adopted the baby raccoon. Last week, DHEC would only say that the animal was found on Hilton Head. The state agency has now evaluated 33 Okatie and Georgia residents for possible exposure to the rabid animal, said DHEC spokeswoman Clair Boatwright. Initially, 16 people had come in contact with the animal through kissing, holding, and feeding it by putting their fingers in its mouth, DHEC said. Now, 24 are getting vaccinated to prevent them from contracting rabies, DHEC said on 13 May 2008. The other nine were exposed to the raccoon but did not need treatment. Boatwright said those nine did not touch the animal but were part of the investigation. Boatwright said 17 pets belonging to the exposed humans are under quarantine for 45 days.

The people who found the raccoon in the woods at Wexford passed it around to many of their friends and relatives, Boatwright said. “They found it, took it to somebody else who kept it for a few days, and thought someone else would want it,” she said. “It was the pass-around-pack for a while from what we understand.”
(ProMED 5.15.08)

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USA (Colorado): Kiowa county man dies from hantavirus infection
Rural residents received a warning on 7 May 2008 when Fremont County public health officials announced the first local case of hantavirus, which is fatal in nearly half of all cases. A Kiowa County, Colorado resident died from the disease in February 2008. The virus is carried in the saliva, urine, and droppings of deer mice (Peromyscus maniculatus), which are found in rural areas and pose a significant risk when residents perform spring cleaning and open up cabins, buildings, sheds, and barns. “Before people begin cleaning out building structures that have been closed up all winter, they need to take precautions,” said Clarice Little, Fremont County public health administrator, “particularly if there are accumulations of mouse droppings and other signs of mice.”

Infection occurs when the virus becomes airborne and is inhaled, or by direct contact with rodents, their droppings, or nests. Vacuuming an area without first wetting it down does not provide protection. Little said the disease cannot be transmitted from person to person. No effective treatment exists for the disease, Little said, so prevention is the key to avoiding hantavirus (infection).

“When hantavirus infection is suspected or confirmed, early admission to a hospital where careful monitoring, treatment of symptoms, and supportive therapy can be provided is most important,” Little said. Homes can be rodent-proofed by eliminating food sources for rodents and removing abandoned vehicles, wood, brush, and junk piles where rodents hide, Little said. She urged caution around mouse droppings and other evidence of mice. A large, rapid increase in the number of mice around a home often precedes a human case of the virus.
(ProMED 5.12.08)

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USA (New York): Health officials attempt to raise awareness of shigellosis
The Health Department on 2 May 2008 notified Orthodox Jewish residents of the Borough Park and Williamsburg communities in Brooklyn of an ongoing outbreak of shigellosis, an intestinal infection. So far in 2008, the two communities have had more than 150 cases of shigellosis, more than half of them among very young children. In the hardest-hit area (zip code 11219) 60 people have been infected. The Health Department is working with community leaders, including rabbis and City Council members, to raise awareness of the outbreak and to provide advice on prevention.

Shigellosis spreads easily among young children in day care and preschool environments. Parents, teachers and caregivers should help young children wash their hands thoroughly and should make sure it is done properly. It takes very few Shigella bacteria to cause illness.

“We encourage residents to be vigilant about hand-washing,” said Dr. Sharon Balter, Medical Epidemiologist in the Health Department's Bureau of Communicable Disease. Large outbreaks of shigellosis have occurred in recent decades in traditionally observant Jewish communities in Borough Park, Williamsburg and other parts of New York State, New Jersey, Illinois, Maryland and Canada. Some 274 cases of shigellosis were reported in New York City in 2006, a rate of 3.4 cases per 100,000 people.
(ProMED 5.8.08)

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USA (Washington): Measles outbreak continues in Grant County, possible exposure in King County
A ninth case of measles has been confirmed in Grant County in Eastern Washington, and it’s possible some people in King County also may have been exposed. The latest case is in a female student at Moses Lake Christian Academy.

All activities at the school have been cancelled until further notice while officials work to identify students and school staff who may be at risk of infection. The girl traveled to western Washington on 29 Apr 2008 as part of a school trip and would have been contagious at the time. The other eight cases were in members of a family from Grant County who attended a “Generation Church Conference” in Kirkland in late March 2008 and developed symptoms afterwards.

In 2000, the Centers For Disease Control (CDC) declared measles had been eliminated in the United States, but now the CDC says 64 cases have been reported in nine states in 2008. The agency says that’s the highest number they’ve seen in seven years. All of the patients except one weren’t vaccinated. States most affected were Wisconsin, Arizona, Michigan and New York.
(ProMED 5.5.08)

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Canada: Health authorities worry as measles outbreak continues
A measles outbreak has reared its ugly head in Toronto again, with four new cases reported to Public Health in the past few days. Initial reports of the illness surfaced in early spring 2008. Since the start of the investigation into the sudden breakout nine cases have now been reported. Outbreaks have also been noted in other parts of Ontario, as well as in Europe and the United States.

But these new cases are more worrisome for authorities. Two of them were traced back to patients who had been at the Scotia and TD Towers, potentially leaving those who frequent the underground PATH system (a 27-kilometer network of pedestrian tunnels beneath the office towers of downtown Toronto) exposed.

“All of the new cases either live or work downtown,” reveals Dr. Barbara Yaffe, director of Communicable Disease Control for Toronto Public Health. “Anyone born before 1970 likely had measles in childhood, and is therefore protected. Everyone else should ensure they have had two doses of measles vaccine for full protection, especially as we know measles is circulating in Toronto.” Toronto Public Health is recommending that those who received a single vaccination as children consider getting a second dose. “Complete and up-to-date vaccination remains the best way to protect yourself and your family from communicable diseases like measles,” Dr. Yaffe added. “Prior to universal immunization in the 1970s, Canada saw thousands of cases of measles each year.”
(ProMED 5.9.08)

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3. Updates
AVIAN/PANDEMIC INFLUENZA

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Hand, foot and mouth disease – *Major International Outbreak*
China
The death toll rose to 43 from the hand, foot, and mouth disease virus that has sickened tens of thousands of children across China, a report said on 16 May 2008. As of 14 May 2008, the hand, foot, and mouth disease virus had sickened more than 24,934 children in seven Chinese provinces plus Beijing.

The number is expected to continue rising after the state Health Ministry ordered health care providers to report cases within 24 hours. The virus has been yet another major concern for Chinese authorities as they prepare for the Beijing Olympics in August 2008. Cases have been reported from Guangdong province in the south to Jilin province in the northeast, and in major cities including Beijing and Shanghai.

Most cases of hand, foot, and mouth disease in China this year have been blamed on Enterovirus 71. The virus spreads through contact with saliva, feces, nose, and throat mucus or fluid secreted from blisters. There is no vaccine or specific treatment, but most children with mild forms of the illness recover quickly after suffering little more than a fever and rash. The disease is expected to peak in the hot months of June and July.
(Associated Press 5.16.08)

Malaysia
Sarawak is stepping up prevention and control measures for hand, foot, and mouth disease (HFMD) following recent outbreaks in Singapore and China. Deputy Chief Minister Tan Sri Dr. George Chan said the state health department's routine HFMD surveillance showed that 1,729 cases of the disease had been reported as of 26 Apr 2008, including three small, localized outbreaks.

The first occurred at Universiti Malaysia Sarawak (Unimas) on 10-25 Mar 2008 involving 48 adults, the second in Kampung Pichin, Serian (4-22 Apr 2008) involving 24 children and the last at Al Hidayah Abim Nursery in Sarikei (9-24 Apr 2008) involving 10 children. Dr. Chan said none of the cases involved enterovirus 71 (EV71), which potentially causes a more severe form of the disease.

“The outbreaks were mild and no one was hospitalized. All the outbreaks have now been controlled. However, because of the increased number of cases in Singapore including a few with EV71, and also in Anhui, China. . .this is a good time to warn the public, especially those looking after young children, to make sure they follow hygienic practices,” he told a press conference at his office here on 2 May 2008. Sarawak last experienced a major outbreak of HFMD in 2006, when more than 14,000 cases and 13 deaths were reported.
(ProMED 5.2.08)

Mongolia
Some 294 suspected hand, foot, and mouth disease (HFMD) cases had been detected in Mongolia by 12 May 2008. Mongolian officials said 134 out of the suspected 294 patients have been hospitalized, and the others, who have milder symptoms, are quarantined at home. There have been no reported deaths so far. Mongolia has set up an emergency committee headed by Deputy Prime Minister Miegombyn Enkhbold to take measures to prevent the spread of the epidemic. Elementary schools in the country have suspended classes starting on 12 May 2008. The first suspected HFMD case in Mongolia was reported on 8 May 2008 in the Mongolian capital (Ulaanbaatar).
(ProMED 5.13.08)

Taipei
Public health officials reported the death of a three-year-old boy in southern Kaohsiung on 5 May 2008; the second fatal enterovirus case this year. They urged all parents and schoolteachers to be more vigilant against enterovirus (infection), as temperatures in Taiwan continue to rise into the summer months. Chou Jih-haw, deputy director of the Center for Disease Control (CDC) under the Department of Health (DOH), said that the latest victim was a boy aged three years and four months who had probably been infected by his five-year-old sister. On 11 Apr 2008, the boy developed a fever, with rashes and sores in his mouth, and he was checked into the hospital with spasms on 12 Apr 2008, Chou said. The boy lapsed into a coma shortly after he was admitted, and died five days later despite efforts to save him, Chou said. An investigation found that the boy's sister also had an enterovirus infection, and had been admitted to the hospital on 13 Apr 2008. But she fully recovered because her case was not that serious.

Health officials at the CDC said that the number of confirmed serious cases of enterovirus has reached 60 in 2008, and among them there have been two deaths; seven other patients remain in intensive care, while one has been hospitalized for about four months due to encephalitis complications.
(ProMED 5.6.08)

Singapore
Infections continue to rise in Singapore, which has reported more than 9,000 cases (HFMD) in 2008, with EV-71 found in 25 percent of the samples tested. No deaths have been reported in the wealthy city-state, but the government has ordered 11 preschools and child-care centers closed, according to the Health Ministry's Web site.
(ProMED 5.4.08)

Viet Nam
“On average, several children die from the disease [HFMD] each month at the hospital,” said Dr. Nguyen Quang Vinh at Children's Hospital No. 1 in Viet Nam’s southern Ho Chi Minh City. "Those children die not because they are admitted to the hospital late, but because their disease develops fast and attacks the brain and heart." The number of cases reported nationwide in 2008 in Viet Nam was not immediately available, but state-run media have reported that some children's hospitals have seen increases of up to seven times over the number of 2007 cases.
(ProMED 5.4.08)

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DENGUE
Hong Kong
The Centre for Health Protection has confirmed 2008's 11th dengue fever case involving a 30-year-old man who fell sick after visiting the Maldives. He traveled to the Maldives on 5-13 Apr 2008 and developed a fever, sore throat, runny nose, and rash on 18 Apr 2008. He was admitted to Princess Margaret Hospital four days later and was discharged on 27 Apr 2008. In 2007, 58 dengue cases were reported in Hong Kong and all of them were classified as imported cases.
(ProMED 5.5.08)

Indonesia
Dengue fever in East Kalimantan has killed 10 people each month in 2008. Up to 28 Apr 2008, dengue has caused 41 fatalities. The local government up to now has not determined whether there was an extraordinary incident in this case. “Mostly, patients died because they were handled too late,” said Parmono Kepala Sub Bidang Penanggulangan of Infectious Diseases in the Health Service of East Kalimantan. According to the data of the Health Service, during 2008 up until 28 Apr 2008, 2396 dengue patients have been attended to. Of this number, 41 people died. Balikpapan city was recorded as the area having the most dengue patients, with 865, 13 of whom died. This area was followed by Samarinda, with 743 patients and 10 deaths, and the Kutai Kartanegara region, with 231 patients and 8 deaths.

Also, in Sukoharjo District, Central Java province during April 2008, two children died of dengue fever. In the first quarter of 2008, there were a total of 160 dengue fever cases and seven residents died of the disease in the district, Agus Prihatmo of the Sukohardjo health service said on 1 May 2008. Most of the victims were children and they lost their lives because they had been admitted to the hospital in very critical condition, he said, (and added that there is a) lack of awareness in the community on the eradication of mosquito-nesting (breeding) grounds, making the areas prone to dengue fever caused by Aedes aegypti mosquito bites.
(ProMED 5.5.08 & 5.13.08)

Malaysia
Malaysia has been fighting the dengue scourge for more than four decades, yet the number of cases is increasing. “We have been fogging and fogging for the last 30 years, and if the number (of cases) is steadily increasing over the years, surely something is not right?” said Professor Dr Sazaly Abu Bakar, director of the WHO Collaborating Centre for Arbo-virus Research and Reference (Dengue Fever/Dengue Haemorrhagic Fever) at Universiti Malaya.

Dr Sazaly said Malaysians had grown complacent because the dengue problem had not been prevalent in the country for so long. For example, the current vector-controlling measures were adopted from an American model developed some 30 years ago, and it (fogging) was only effective in killing the adult mosquitoes but not the larvae, said Dr Sazaly, who also heads the Department of Medical Microbiology at Universiti Malaya. “No one knows the answers, because we have not done any studies. We need to study these factors and devise a strategy based on it.” Dr Sazaly said one of the more effective ways to control the problem was for the authorities to take daily and weekly samples of mosquitoes to find those carrying the dengue virus and reduce their population without disturbing the ecological system. “There should be continuous monitoring and surveillance, and only then can we predict and preempt an outbreak before it occurs. Right now, we do not even know the genetics of our mosquitoes here. The fire-fighting methods, such as fogging an area when a case is reported, are ineffective.”

In Malaysia, the number of dengue fever and dengue haemorrhagic fever cases has risen from 518 cases in 1973 to 45,856 suspected cases in 2007.

“The danger is that for every patient confirmed with dengue, three more go undetected because it is asymptomatic.” Dr Sazaly said there was a need to come up with a faster and more accurate method of diagnosing dengue. “We are still relying on old lab tests which require you to have a fever for at least five days before you are confirmed to be positive for dengue. By then, your condition may be severe, and by the time you go to hospital, it may be too late. We have to improve not only our vector-control methods but also ensure early detection of the infection, like coming up with a cheap self-diagnostic kit.” Dr Sazaly said although the technology was available now, it was expensive and could only be done at referral centers such as the University Malaya Medical Centre and the Kuala Lumpur Hospital. “We need to come up with our own diagnostic kit so that we can bring the cost down.”

He said of the 45,856 suspected dengue cases in 2007, only 14,354 were confirmed positive by laboratory test. “Because of the weaknesses in our detection system, we could not positively identify the remaining 33,000 as dengue cases. So, these people who are walking out there could have been infected and not know it. People need to know their dengue status. If you have had dengue fever before, then you have to be careful, because the second time you get it, the chances are high that it will develop into haemorrhagic fever. But then again, not everyone who has a second infection will die. We need to study the factors which contribute to dengue haemorrhagic fever and determine those who are more susceptible.”

Those who are obese, diabetic or over 60 years old are considered to be in the high-risk group, as they have a higher chance of developing dengue haemorrhagic fever. “We need to study why this group is predisposed to it, and, to do this, we need to study their genetic background. If we know that not everyone will die of dengue, at least we can focus on the type of patients we need to manage. If we can spend some money to research this, we can develop drugs to prevent these deaths. And if we have drugs to manage dengue, we won't have to vaccinate 29 million people.”

He said it was not cost-effective to develop a vaccine for a large number of people when only a certain percentage of them were at real risk of dying from dengue. Dr Sazaly said the proper management of dengue patients was another area that was often overlooked by doctors. As there is no blanket treatment that is suitable for all dengue patients, doctors need to treat each patient based on the symptoms. Dr Sazaly said a multi-pronged approach was needed to tackle the dengue problem, including funding more research by local scientists. “It is hyper-endemic here, and yet we are not putting our research efforts into it.”
(ProMED 5.13.08)

Peru
During the week of 20-26 Apr 2008, the office of the director general of epidemiology (DGE) reported 138 cases of classical dengue; 73 percent of these cases were reported by 16 regional health directorates. The reported national cumulative total (of dengue cases) was 6,409, of which 1,126 were laboratory confirmed; 4,070 were probable (cases) and 1,213 were discarded. Up to the week of 20-26 Apr 2008, 25 DHF cases have been reported, nine of which were confirmed. No deaths have been reported due to DHF. The national cumulative incidence is 18.67 dengue cases per 100,000 inhabitants. The risk of infection is greatest in the eastern and northeastern tropical Amazon drainage departments (state/province equivalents).
(ProMED 5.13.08)

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4. Articles
Enterovirus Déjà Vu
Modlin JF, et al. New England Journal of Medicine. 2007;356:1204-1205
http://content.nejm.org/cgi/content/short/356/12/1204

Introduction
More than 90 human enterovirus serotypes have now been identified in three distinct waves of discovery. The three poliovirus serotypes were first isolated from nonhuman primates in the course of painstaking experiments performed during the first half of the 20th century. The use of small laboratory animals and the advent of cell culture in mid-century led to the description of 61 more enteroviruses that we know as coxsackieviruses, echoviruses, and the newer enteroviruses. The application of polymerase chain reaction and genomic sequencing has recently permitted characterization of approximately 30 previously unidentified enterovirus serotypes and undoubtedly will uncover more.

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An eight-year study of epidemiologic features of enterovirus 71 infection in Taiwan
Chen SC, et al. American Journal of Tropical Medicine and Hygiene. 2007 Jul;77(1):188-91.

Abstract
In 1998, an epidemic of enterovirus 71 (EV 71) infection occurred in Taiwan. The purpose of this study was to assess the epidemiology of EV 71 infection in Taiwan. Between March 1998 and December 2005, a total of 1,548 severe cases of hand, foot, and mouth disease and herpangina (HFMD/HA) was reported to the Center for Disease Control in Taiwan. A seasonal variation in number of severe cases was observed, with the annual peak in second quarter. Deaths from severe HFMD/HA varied from year to year (chi(2) for trend = 6.781, P = 0.009). Most (92%) cases occurred in children ^top

Salmonellosis Outcomes Differ Substantially by Serotype
Jones TF, et al. The Journal of Infectious Diseases 2008;198:000–000
http://www.journals.uchicago.edu/doi/abs/10.1086/588823

Background
Most human infections are caused by closely related serotypes within 1 species of Salmonella. Few data are available on differences in severity of disease among common serotypes.

Methods
We examined data from all cases of Salmonella infection in FoodNet states during 1996-2006. Data included serotype, specimen source, hospitalization, and outcome.

Results
Among 46,639 cases, 687 serotypes were identified. Overall, 41,624 isolates (89%) were from stool specimens, 2524 (5%) were from blood, and 1669 (4%) were from urine; 10,393 (22%) cases required hospitalization, and death occurred in 219 (0.5%). The case fatality rate for S. Newport (0.3%) was significantly lower than for Typhimurium (0.6%); Dublin (3.0%) was higher. With respect to invasive disease, 13 serotypes had a significantly higher proportion than Typhimurium (6%), including Enteritidis (7%), Heidelberg (13%), Choleraesuis (57%), and Dublin (64%); 13 serotypes were significantly less likely to be invasive. Twelve serotypes, including Enteritidis (21%) and Javiana (21%), were less likely to cause hospitalization than Typhimurium (24%); Choleraesuis (60%) was significantly more so.

Conclusions
Salmonella serotypes are closely related genetically yet differ significantly in their pathogenic potentials. Understanding the mechanisms responsible for this may be key to a more general understanding of the invasiveness of intestinal bacterial infections.
(CIDRAP 5.6.08)

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Crystal structures of oseltamivir-resistant influenza virus neuraminidase
Collins PJ, et al. Nature advance online publication 14 May 2008
http://www.nature.com/nature/journal/vaop/ncurrent/abs/nature06956.html

Abstract
The potential impact of pandemic influenza makes effective measures to limit the spread and morbidity of virus infection a public health priority. Antiviral drugs are seen as essential requirements for control of initial influenza outbreaks caused by a new virus, and in pre-pandemic plans there is a heavy reliance on drug stockpiles. The principal target for these drugs is a virus surface glycoprotein, neuraminidase, which facilitates the release of nascent virus and thus the spread of infection. Oseltamivir (Tamiflu) and zanamivir (Relenza) are two currently used neuraminidase inhibitors that were developed using knowledge of the enzyme structure. It has been proposed that the closer such inhibitors resemble the natural substrate, the less likely they are to select drug-resistant mutant viruses that retain viability. However, there have been reports of drug-resistant mutant selection in vitro and from infected humans. We report here the enzymatic properties and crystal structures of neuraminidase mutants from H5N1-infected patients that explain the molecular basis of resistance. Our results show that these mutants are resistant to oseltamivir but still strongly inhibited by zanamivir owing to an altered hydrophobic pocket in the active site of the enzyme required for oseltamivir binding. Together with recent reports of the viability and pathogenesis of H5N1 and H1N1 viruses with neuraminidases carrying these mutations, our results indicate that it would be prudent for pandemic stockpiles of oseltamivir to be augmented by additional antiviral drugs, including zanamivir.
(CIDRAP 5.15.08)

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Cross-Recognition of Avian H5N1 Influenza Virus by Human Cytotoxic T-Lymphocyte
Kreijtz JH, et al. Journal of Virology. 2008;82(11):5161-5166
http://jvi.asm.org/cgi/content/abstract/82/11/5161

Abstract
Since the number of human cases of infection with avian H5N1 influenza viruses is ever increasing, a pandemic outbreak caused by these viruses is feared. Therefore, in addition to virus-specific antibodies, there is considerable interest in immune correlates of protection against these viruses, which could be a target for the development of more universal vaccines. After infection with seasonal influenza A viruses of the H3N2 and H1N1 subtypes, individuals develop virus-specific cytotoxic T-lymphocyte responses, which are mainly directed against the relatively conserved internal proteins of the virus, like the nucleoprotein (NP). Virus-specific cytotoxic T lymphocytes (CTL) are known to contribute to protective immunity against infection, but knowledge about the extent of cross-reactivity with avian H5N1 influenza viruses is sparse. In the present study, we evaluated the cross-reactivity with H5N1 influenza viruses of polyclonal CTL obtained from a group of well-defined HLA-typed study subjects. To this end, the recognition of synthetic peptides representing H5N1 analogues of known CTL epitopes was studied. In addition, the ability of CTL specific for seasonal H3N2 influenza virus to recognize the NP of H5N1 influenza virus or H5N1 virus-infected cells was tested. It was concluded that, apart from some individual epitopes that displayed amino acid variation between H3N2 and H5N1 influenza viruses, considerable cross-reactivity exists with H5N1 viruses. This preexisting cross-reactive T-cell immunity in the human population may dampen the impact of a next pandemic.
(CIDRAP 5.14.08)

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Multi-antigen vaccines based on complex adenovirus vectors induce protective
Holman DH, et al. Vaccine. 2008;26(21):2627-39. Epub 2008 Mar 14.

There are legitimate concerns that the highly pathogenic H5N1 avian influenza virus could adapt for human-to-human transmission and cause a pandemic similar to the 1918 “Spanish flu” that killed 50 million people worldwide. We have developed pandemic influenza vaccines by incorporating multiple antigens from both avian and Spanish influenza viruses into complex recombinant adenovirus vectors. In vaccinated mice, these vaccines induced strong humoral and cellular immune responses against pandemic influenza virus antigens, and protected vaccinated mice against lethal H5N1 virus challenge. These results indicate that this multi-antigen, broadly protective vaccine may serve as a safer and more effective approach than traditional methods for development of a pandemic influenza vaccine.
(CIDRAP 5.14.08)

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5. Notifications
APEC EINet Pandemic Influenza Preparedness Virtual
APEC EINet is pleased to host a special videoconference on pandemic influenza preparedness. This videoconference is a follow-up to our first “virtual symposium”, which was conducted in January 2006 with great success (participating economies were Australia, Canada, China, Korea, Philippines, Singapore, Chinese Taipei, Thailand, USA, and Viet Nam). You can view a five-minute videoclip of our previous virtual symposium at: http://depts.washington.edu/einet/symposium.html. Our upcoming videoconference will be held in late May 2008. It will take place during the evening hours of 29 May in the Americas and in the morning hours of 30 May in Asia, for approximately 5 hours. Our objective is to describe how private and public sectors in the APEC region can cooperate and work effectively to prepare for and respond to an influenza pandemic.

Through this videoconference, we hope to promote regional information sharing and collaboration to enhance pandemic preparedness. In order to improve preparedness regionally, it is vital to understand how each economy in the region is undertaking this task. In this process, EINet will:

  1. Bring together economies in a dynamic, real-time discussion on preparedness through the collaboration of the health and the business/trade sectors, with a focus on critical systems continuity.
  2. Share specific examples of current practices—e.g. scenario exercises, communication drills and policy evaluation.
  3. Use innovative technologies (e.g. Access Grid) for real-time, virtual interchange, enhancing their utility for future collaboration and response in the event of a pandemic.
Videoconferencing offers an alternative to in-person conferencing. It cuts down on the time and cost of traditional conferences requiring long-distance travel. Simultaneous communication with multiple sites is possible, with numerous visualization options. Real-time web-based information exchange is also possible, and, during an actual pandemic, the virtual medium would be a safe way to communicate when international travel is limited or prohibited.

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Critical care panel tackles disaster preparation, surge capacity, rationing
http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/may1308chest.html

Anticipating that a terrorist attack, influenza pandemic, or natural disaster will someday exhaust regional or national critical care systems, an expert task force recently issued a comprehensive series of reports that takes stock of current capabilities and recommends a surge framework that would care for as many patients as possible but would necessarily exclude some.

The series, from the Critical Care Collaborative Initiative's January 2007 Mass Critical Care Summit, appeared recently in a May supplement issue of the journal Chest. The five articles from the 37-member task force of American and Canadian experts include an executive summary and individual papers on current capabilities, a framework to optimize surge capacity, medical resource guidance, and recommendations for allocating scarce critical care resources in a mass critical care setting.

Task force member John Hick, MD, said that, although initial mainstream media focus was patient exclusion issues surrounding the task force’s ventilator triage criteria, the guidelines are so far receiving good support in the medical community. "It [the series] provides both a systems and facility-based approach to resource-poor situations," he said. "Whether the goals are reasonable or not, we'll have to see," added Hick, medical director of bioterrorism and disaster preparedness and an emergency medicine physician at Hennepin County Medical Center in Minneapolis and coauthor on three of the five articles.

Though the group covered an expansive array of controversial ethics and resource topics related to critical care in a disaster scenario, they had few disagreements on about 90% of the materials, Hick said. Not surprisingly, the critical care inclusion-exclusion generated the most discussion and required a great deal of compromise, he said. “It’s not exactly what we would do as individuals, but it’s a good framework nonetheless,” Hick said. Perhaps the biggest sticking point was the group’s recommendation for intensive care unit (ICU) expansion, he said, adding that the group settled on 200% because of pandemic concerns, though many advocated 100% ICU expansion as a more achievable goal. “My only fear is that people will see that as unrealistic and not aim for what they can achieve, and I think we tried to be clear to do at least what you can,” Hick said.
(CIDRAP 5.13.08)

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Proposed Guidance on Workplace Stockpiling of Respirators and Facemasks
US Department of Labor — Occupational Safety and Health administration
http://www.osha.gov/dsg/guidance/stockpiling-facemasks-respirators.html

In the event of an influenza pandemic, employers will play a key role in protecting employees’ health and safety as well as in limiting the impact on the economy and society. Employers will likely experience employee absences, changes in patterns of commerce and interrupted supply and delivery schedules. To further preparedness efforts, the Department of Labor (DOL) proposes to publish this information on stockpiling respirators and facemasks in occupational settings as an appendix to the DOL and the Department of Health and Human Services (HHS) jointly issued Guidance on Preparing Workplaces for an Influenza Pandemic (February 2007). This proposed guidance is designed to encourage employers in the private and public sectors to purchase and stockpile facemasks and respirators in advance of an influenza pandemic, because manufacturing capacity at the time of an outbreak would not meet the expected demand for respiratory protection devices during the pandemic. Through advanced planning and stockpiling, employers will be able to better protect their employees as well as lessen the impact of a pandemic on their business, society, and the economy.

As is explained in more detail in this guidance, employers should consider stockpiling facemasks and respirators. More specifically, it is recommended that employees at very-high risk and high risk of exposure to pandemic influenza use respirators, while employees at medium risk of exposure use facemasks. Neither facemasks nor respirators are recommended for employees at lower risk of exposure to pandemic influenza.
(ProMED 5.14.08)

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CDC guide to hand, foot, and mouth disease
http://www.cdc.gov/ncidod/dvrd/revb/enterovirus/hfhf.htm

What is hand, foot, and mouth disease?
Hand, foot, and mouth disease (HFMD) is a common illness of infants and children. It is characterized by fever, sores in the mouth, and a rash with blisters. HFMD begins with a mild fever, poor appetite, malaise (“feeling sick”), and frequently a sore throat. One or 2 days after the fever begins, painful sores develop in the mouth. They begin as small red spots that blister and then often become ulcers. They are usually located on the tongue, gums, and inside of the cheeks. The skin rash develops over 1 to 2 days with flat or raised red spots, some with blisters. The rash does not itch, and it is usually located on the palms of the hands and soles of the feet. It may also appear on the buttocks. A person with HFMD may have only the rash or the mouth ulcers.

Is HFMD the same as foot-and-mouth disease?
No. HFMD is often confused with foot-and-mouth disease of cattle, sheep, and swine. Although the names are similar, the two diseases are not related at all and are caused by different viruses. For information on foot-and-mouth disease, please visit the Web site of the US Department of Agriculture.

What causes HFMD?
Viruses from the group called enteroviruses cause HFMD. The most common cause is coxsackievirus A16; sometimes, HFMD is caused by enterovirus 71 or other enteroviruses. The enterovirus group includes polioviruses, coxsackieviruses, echoviruses and other enteroviruses.

Is HFMD serious?
Usually not. HFMD caused by coxsackievirus A16 infection is a mild disease and nearly all patients recover without medical treatment in 7 to 10 days. Complications are uncommon. Rarely, the patient with coxsackievirus A16 infection may also develop “aseptic” or viral meningitis, in which the person has fever, headache, stiff neck, or back pain, and may need to be hospitalized for a few days. Another cause of HFMD, EV71 may also cause viral meningitis and, rarely, more serious diseases, such as encephalitis, or a poliomyelitis-like paralysis. EV71 encephalitis may be fatal. Cases of fatal encephalitis occurred during outbreaks of HFMD in Malaysia in 1997 and in Taiwan in 1998. Is HFMD contagious? Yes, HFMD is moderately contagious. Infection is spread from person to person by direct contact with nose and throat discharges, saliva, fluid from blisters, or the stool of infected persons. A person is most contagious during the first week of the illness. HFMD is not transmitted to or from pets or other animals. How soon will someone become ill after getting infected? The usual period from infection to onset of symptoms (“period”) is 3 to 7 days. Fever is often the first symptom of HFMD. Who is at risk for HFMD? HFMD occurs mainly in children under 10 years old, but may also occur in adults too. Everyone is at risk of infection, but not everyone who is infected becomes ill. Infants, children, and adolescents are more likely to be susceptible to infection and illness from these viruses because they are less likely than adults to have antibodies and be immune from previous exposures to them. Infection results in immunity to the specific virus, but a second episode may occur following infection with a different member of the enterovirus group.

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 apecein@u.washington.edu