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EINet Alert ~ Jun 01, 2007


*****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:
- Global: Cumulative number of human cases of avian influenza A/(H5N1)
- UK (Wales): H7N2 avian influenza infections reported in 4 humans
- China: New case of avian influenza H5N1 infection in human
- China: Avian influenza H5N1 samples from human cases arrive in US
- Indonesia: Report of fatal case of avian influenza H5N1 infection
- Pakistan (Sihala): Avian influenza infected poultry culled
- Thailand: Avian influenza prevention strategies
- Viet Nam: More avian influenza H5N1 outbreaks among poultry
- Viet Nam: Latest human case of avian influenza awaits WHO confirmation
- Nigeria (Zamfara): Report of avian influenza H5N1 outbreak

1. Updates
- Avian/Pandemic influenza updates

2. Articles
- Avian influenza A/(H7N2) outbreak in the United Kingdom
- Low Pathogenicity Avian Influenzas and human health
- Transparent Development of the WHO Rapid Advice Guidelines
- Prophylactic and Therapeutic Efficacy of Human Monoclonal Antibodies against H5N1 Influenza
- Immunogenicity and Safety of Intradermal Influenza Immunization at a Reduced Dose in Healthy Children
- How can IT respond to a flu pandemic?

3. Notifications
- CDC Guidelines for Large-Scale Influenza Vaccination Clinic Planning
- Pandemic Flu Leadership Blog: HHS forum, runs May 22-June 27
- Guidance for Industry: Clinical Data Needed to Support the Licensure of Seasonal Inactivated Influenza Vaccines
- Technical Meeting on Highly Pathogenic Avian Influenza and Human H5N1 Infection


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

2003
Viet Nam / 3 (3)
Total / 3 (3)

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

2005
Cambodia / 4 (4)
China / 8 (5)
Indonesia / 17 (11)
Thailand / 5 (2)
Viet Nam / 61 (19)
Total / 95 (41)

2006
Azerbaijan / 8 (5)
Cambodia / 2 (2)
China / 13 (8)
Djibouti / 1 (0)
Egypt / 18 (10)
Indonesia / 56 (46)
Iraq / 3 (2)
Thailand / 3 (3)
Turkey / 12 (4)
Total / 116 (80)

2007
Cambodia/ 1 (1)
China / 3 (1)
Egypt / 16 (4)
Indonesia / 23 (20)
Laos / 2 (2)
Nigeria / 1 (1)
Total / 44 (28)

Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 309 (187).
(WHO 5/31/07 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 5/16/07)

WHO's maps showing world's areas reporting confirmed cases of H5N1 avian influenza in humans, poultry and wild birds (last updated 5/31/07):
http://gamapserver.who.int/mapLibrary/

WHO’s timeline of important H5N1-related events (last updated 5/10/07):
http://www.who.int/csr/disease/avian_influenza/ai_timeline/en/index.html.

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Europe/Near East
UK (Wales): H7N2 avian influenza infections reported in 4 humans
4 people have tested positive for the low-pathogenic H7N2 avian influenza subtype found last week in chickens at a small farm in Corwen Farm, Conwy, Wales, and health authorities suspect some degree of human-to-human transmission of the disease. Of the 4 positive results, 2 were from Wales and 2 were from northwest England. England's Health Protection Agency (HPA), in announcing the positive tests 4 days ago, said 5 other patients whose test results were negative for the virus are undergoing treatment as a precaution because they had similar illnesses. All of the patients who tested positive for the virus had contact with infected birds. The poultry outbreak in Wales started 8 May 2007, was laboratory confirmed 24 May 2007, and notified to the World Organisation for Animal Health 25 May 2007.

The National Public Health Service (NPHS) for Wales said that of 221 people who were identified as contacts so far, 12 are ill with conjunctivitis or a nonserious flulike illness. The NPHS said it could not rule out human-to-human spread of the virus but that it had no laboratory confirmation of such cases. "Of the people with conjunctivitis or a flulike illness, some did not have close contact with infected poultry," said Marion Lyons, lead consultant in communicable disease control for the NPHS.

On May 24, 2007 veterinary officials in Wales confirmed a low-pathogenic H7N2 avian influenza outbreak at a farm near the northern town of Denbighshire. Great Britain and Wales contingency plans have been activated. A 1km restriction zone was been set up around the farm, and the restrictions are still in place. For outbreaks of mild strains of avian flu subtypes such as H7N2, public health officials often order culling of birds and monitor human cases because the viruses could mutate into highly pathogenic forms. Welsh veterinary officials think the infected Rhode Island chickens could have been exposed to the virus on May 7 at the Chelford Market in Cheshire. A total of 30 chickens from the smallholding have now been slaughtered after 15 birds died. The owners of the farm tested negative for the virus. Reportedly, tests on birds at another farm in Llyn Peninsula came back negative.

Of 221 patients identified as contacts, 171 may have been exposed in a workplace setting, including patients and staff at 2 hospitals. At one of the hospitals, 79 patients and staff were offered oseltamivir because of contact with a healthcare worker who was treated for the H7 flu virus. Lyons said the sick staff member was working between May 21 and 23, when she may have been infectious. At the other hospital, 69 patients and staff were notified because a patient who had the H7N2 illness was recently treated at the facility. Lyons said the patient was discharged May 18, and after an 8-day incubation period, anyone who was ill would have had symptoms by May 26. "So we are contacting all staff and patients to ensure that they remained well and to reassure them," she said. Lyons said that people who have had contact with individuals who became ill with the H7N2 virus are being offered prophylactic antiviral medication. In a related development, children at a primary school in the town where the Welsh farm is located are reportedly being given Tamiflu after one of their classmates became ill with suspected H7N2 infection. The ill child visited the affected farm 10 days ago for less than 15 minutes.

A case is an individual with influenza-like illness (fever above 38 C, aches and pains, cough/head cold, sore throat or conjunctivitis) who has been in contact with affected premises or with known infected poultry (handling/within one metre) or close contact with another human case. A contact is defined as an individual who has been in contact with affected premises or with known infected poultry (handling/within one meter) or has had close contact with another person with confirmed or presumptive avian influenza). Reportedly, there is enough oseltamivir (Tamiflu) to treat a quarter of the population of Wales.

Some infectious disease experts say human illnesses associated with the H7N2 outbreak in Wales are a reminder that other virus subtypes—not just the well-known H5N1 strain—could spark a pandemic. Other experts say the focus on the H5N1 subtype's pandemic potential is justified. David Halvorson, a veterinarian in avian health at the University of Minnesota in St Paul, said that H5 and H7 subtypes both have the ability to generate a highly pathogenic virus of the same subtype, but there's no way to project when and if such evolution will occur. "Whether that will happen quickly, as it did in Chile or British Columbia, or not happen for over 10 years, as it has not done in New York live bird markets, is not predictable," he said. The WHO's Regional Office for Europe said human illness from other H7 subtypes has occurred in two other instances in the past few years. In 2006 a poultry worker in the UK was diagnosed with conjunctivitis linked to an H7N3 poultry outbreak, and in 2003 an outbreak of highly pathogenic H7N7 in the Netherlands resulted in 86 confirmed cases of mild illness, with 1 death—a veterinarian who died from acute respiratory distress syndrome.

Situation updates are available from the Welsh Assembly Government:
<http://new.wales.gov.uk/news/presreleasearchive/?lang=en>.
(CIDRAP 5/26/07, 5/29/07; Promed 5/25/07, 5/26/07, 5/28/07, 5/29/07)

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Asia
China: New case of avian influenza H5N1 infection in human
WHO confirmed China's latest avian influenza H5N1 case, in a 19-year-old soldier who was apparently being treated in a military hospital. China now has had 25 cases, 15 of them fatal. The patient's H5N1 results were confirmed by China's national laboratory May 23. Before the soldier got sick, he was serving in Fujian province. He experienced fever and pneumonia-like symptoms May 9 and was hospitalized May 14. "There is no initial indication to suggest he had contact with sick birds prior to becoming unwell," WHO reported, adding that the patient's close contacts are under medical supervision and remain well. China has not reported any H5N1 outbreaks in Fujian province poultry this year, but on May 19 the agriculture ministry, in a report to the World Organization for Animal Health (OIE), said an outbreak at a farm in southern Hunan province killed more than 11,000 ducklings and led to the culling of 9,600 more.

A woman who was diagnosed with avian influenza Feb 2007 has left the hospital, according to reports from China. The patient is a 44-year-old woman who farms in Fujian province. On Mar 1, 2007, WHO confirmed her as China's 23rd avian flu case-patient. She got sick Feb 18 and had been in critical condition. Reportedly she kept poultry in her back yard, but it was not determined whether she was exposed to sick birds. She was released after 3 months in the hospital. "A doctor in her village will carry out medical checks every day and report her condition to us to ensure her complete recovery," Huang Jian, deputy director of the health bureau in the town of Jianou, where the woman lives, said.
(CIDRAP 5/29/07, 5/30/07)

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China: Avian influenza H5N1 samples from human cases arrive in US
Some of the H5N1 avian flu virus samples from human cases that China has promised to send to a WHO laboratory have arrived in the US, apparently ending an almost year-long lapse in sample sharing. A WHO official said 2 of 3 promised samples have been sent by China's health ministry and are awaiting customs clearance. Joanna Brent, a spokesperson in the WHO's Beijing office, said the specimens are from a 2006 case from Xinjiang province and a 2007 case from Fujian province. Reportedly, a third sample China promised—from a 24-year-old soldier who died in 2003—was not part of the shipment, because sample-sharing procedures involving the Chinese military are extremely complex. In Mar 2006, China promised to send 20 veterinary H5N1 samples to the US CDC for analysis, but their arrival was delayed for several months because of logistical problems. Reportedly CDC did receive the promised specimens. WHO has coordinated the international sharing of flu virus samples for more than 50 years. Samples of both seasonal flu viruses and novel strains like H5N1 are used to monitor viral evolution and drug resistance and to develop vaccines. At the annual World Health Assembly, WHO approved a resolution to establish an international stockpile of pandemic vaccines and create a working group to draw up new rules for the sharing of flu viruses by WHO collaborating centers and reference laboratories.
(CIDRAP 5/25/07)

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Indonesia: Report of fatal case of avian influenza H5N1 infection
Health officials in Indonesia reported that a 45-year-old man from Grobogan district, Central Java province died of H5N1 avian influenza, marking the country's second fatal case in less than 2 weeks. He developed symptoms 17 May 2007, was hospitalized 26 May 2007, and died in hospital 28 May 2007. Investigators, saying dead poultry were found near the man's home, believe he slaughtered and ate a sick chicken. The latest previous case reported in Indonesia was in a 5-year-old girl who died May 17. The country leads the world in human H5N1 cases and deaths. On May 16 the WHO announced it would accept H5N1 test results from Indonesia's newly accredited national laboratory. Of the 98 cases confirmed to date in Indonesia, 78 have been fatal.
(CIDRAP 5/30/07; Promed 5/31/07)

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Pakistan (Sihala): Avian influenza infected poultry culled
The health department in Islamabad detected bird flu at 2 more poultry farms in Sihala and culled 4000 chickens, local media reported 24 May 2007. The authorities found bird flu at 3 poultry farms in Chak Shahzad 23 May 2007 and 12 000 chickens were culled. National Institute of Health Director General Masood Anwar said there had been no human bird flu virus cases so far. He added that the NIH [Pakistan National Institute of Health] had tested 3 men for bird flu but the results were negative. An official of the Ministry of Livestock said that 16 000 chickens had been culled so far to avoid the spread of bird flu. Pakistan's last outbreak was in April 2007.

Excerpts from OIE report:
Information received 25/05/2007 from Animal Husbandry Commissioner/CVO Government of Pakistan, Livestock Wing, Ministry of Food, Agriculture and Livestock.

Start date 01 Feb 2007; Date of confirmation of event 4 Feb 2007; Date of previous occurrence July 2006
Causal agent: Highly pathogenic avian influenza virus H5N1.
Outbreak 1. Sheikh Shahid P/F, Chak Shahzad, Islamabad, Islamabad Capital Territory
Outbreak 2. Chak Shahzad, Islamabad, Islamabad Capital Territory
Outbreak 3. Ashiq P/F, Chak Shahzad, Islamabad, Islamabad Capital Territory
Outbreak 4. Mehmood P/F, Chak Shahzad, Islamabad, Islamabad Capital Territory

Summary of outbreaks Total outbreaks: 4. Total animals affected: Susceptible 17324; Cases 5627; Deaths 5627; Destroyed 11 697; Slaughtered 0. Apparent morbidity rate 32.48 percent; Apparent mortality rate 32.48 percent; Apparent case fatality rate 100.00 percent; Proportion susceptible removed 100.00 percent. Epidemiology Source of infection: Contact with wild Species. A ring vaccination with an H5 inactivated monovalent vaccine in a 3-km-radius zone around the outbreaks is ongoing.
(Promed 5/26/07; CIDRAP 5/25/07)

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Thailand: Avian influenza prevention strategies
Thailand is working on effective strategies to prevent an avian influenza outbreak and respond to the continuing possibility of a bird flu pandemic. Presiding a seminar to draft Thailand's 2008-2010 avian flu and influenza prevention strategy, Deputy Prime Minister Paiboon Wattanasiritham, said agencies concerned must take seriously their responsibility to brainstorm ideas to achieve 4 target strategies -- to control any bird flu outbreak among poultry, to prevent the spread of influenza between humans, to improve surveillance and medical treatment, and to create systematic cooperation. The new strategies will be proposed to the cabinet for approval, together with a requested budget of Thai Baht 10 billion [USD 304 million] to implement the plan. The public health ministry projected that, if the H5N1 mutates into a form that spreads easily among humans, there could be millions of infections and the number of deaths could reach 143 000. Last week the government approved a budget of Thai Baht 1.5 billion [approx. USD 45.6 million] to manufacture flu vaccines to be prepared in case of an emergency situation. Thailand's last outbreak of HPAI H5N1 was recorded in January 2007.
(Promed 5/28/07)

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Viet Nam: More avian influenza H5N1 outbreaks among poultry
Avian influenza has killed hundreds of ducks in 2 farms in northern and southern Viet Nam in the past 2 days, the Agriculture Ministry said 31 May 2007. On 29 May 2007, 115 ducks died at a farm in the southern Mekong delta city of Can Tho and 150 ducks died in the northern province of Quang Ninh 30 May 2007. Tests confirmed the H5N1 virus in both cases, the Animal Health Department said. The 2 flocks had not been vaccinated against bird flu and animal health workers slaughtered the remaining 685 ducks there. The number of birds killed by the virus and slaughtered in May 2007 is more than 50 000 nationwide. Quang Ninh province and Can Tho city are among the 12 localities that reported bird flu outbreaks in poultry this month, at the beginning of summer, which is unusual as experts say the virus thrives best in cool temperatures.

While more than half of Viet Nam's 64 provinces and cities have completed the first phase of poultry vaccinations against bird flu, all the infections found so far were among those which were left out of the nationwide campaign. Agriculture Minister, Cao Duc Phat, said 29 May 2007 that all waterfowl must be vaccinated or slaughtered to help stop bird flu from spreading. The virus has infected ducks and chickens at the beginning of summer, which is unusual as experts say the virus appears to thrive best in cool temperatures and weakens in warmer weather. Many of the provinces that have detected the infection May 2007 are along the national north-south Highway One, suggesting poultry movement should be tightened further to keep the virus from spreading, officials said. International public health officials describe Viet Nam's mass poultry vaccination programme and other measures as a model for keeping the virus at bay.

Avian influenza has hit 12 Vietnamese cities and provinces, namely Quang Ninh, Son La, Nam Dinh, Hai Phong, Bac Giang, Ninh Binh, Bac Ninh, Ha Nam, and Vinh Phuc in the northern region, Nghe An in the central region, and Can Tho and Dong Thap in the southern region. Viet Nam sent its most recent follow-up highly pathogenic avian influenza report to the OIE 24 May 2007, referring to 8 new outbreaks reportedly starting between 9 and 19 May 2007, in the following provinces: Nam Dinh (3 outbreaks), Quang Ninh (2), Dong Thap (1), Can Tho City (1), and Son La (1). Reportedly, fowls have died en masse in Viet Nam's central Quang Ngai province and the 2 northern provinces of Thai Nguyen and Thanh Hoa over the past few days. The fowls might have died as a result of infection by bird flu virus strain H5.
(Promed 5/28/07, 5/30/07, 5/31/07)

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Viet Nam: Latest human case of avian influenza awaits WHO confirmation
A 30-year-old man of northern Vinh Phuc province, who exhibited bird flu symptoms 10 May 2007, after slaughtering chickens for a wedding party, has recently been confirmed by Viet Nam's Health Ministry as the country's first bird flu patient since mid-Nov 2005. Not needing a respirator any more, he is now reportedly recovering at the Bach Mai Hospital in Hanoi capital. WHO said it was working with the government to investigate the case and needed to verify the virus sample. It said finding the suspected patient was not alarming if it was an isolated case.

On 31 May 2007, a local newspaper quoted an official as saying that a change in the bird flu virus strain H5N1 has diminished the effectiveness of vaccines against the disease among poultry. Avian influenza vaccines are produced according to the gene type Z found in bird flu virus strain H5N1 in 2003, when Viet Nam was first hit by the disease, but another gene type called G was detected in 2005, said Nguyen Tien Dung, head of the Ultra-Virus Department of the Veterinary Institute under the Ministry of Agriculture and Rural Development. The types Z and G genes are not very similar, so the vaccines are more effective [against] type Z, and less effective [against] type G, he said, noting that the first infected poultry with the type G gene in Viet Nam were mainly smuggled. According to the ministry's Department of Animal Health, Viet Nam is strengthening bird flu vaccination among fowls nationwide, using vaccines imported mainly from China and the Netherlands.
(Promed 5/28/07, 5/30/07, 5/31/07)

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Africa
Nigeria (Zamfara): Report of avian influenza H5N1 outbreak
Health authorities reported 23 May 2007 an outbreak of the H5N1 bird flu virus in Nigeria's northern state of Zamfara. The virus was confirmed through tests on affected birds in Namaturu village and more than 200 birds had been culled to curtail the spread of the disease, said Aminu Abdulrazak from the state health ministry. The whole area had been disinfected and villagers had been advised to follow advice from doctors. Nigeria, Africa's most populous nation with some 140 million people, earlier in 2007 reported west Africa's first human bird flu death. A 22-year-old woman died in Lagos on 17 Jan 2007, weeks after plucking and disembowelling a chicken. Bird flu was first detected in Nigeria on a farm in Jaji town outside the northern city of Kano in Feb 2006 from where it spread to other parts of the country. Kano, northern Nigeria's most populous city, was worst affected by the flu outbreak which ravaged 97 farms in the city resulting in the death or culling of at least 300 000 birds, officials said. Katsina, Sokoto and Bauchi, 3 other northern states, have recorded a resurgence of bird flu since it resurfaced in Kano.
(Promed 5/26/07)

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1. Updates
Avian/Pandemic influenza updates
- UN: http://influenza.un.org/. UN response to avian influenza and the pandemic threat. Also, http://www.irinnews.org/Birdflu.asp provides information on avian influenza in order to help the humanitarian community.
- WHO: http://www.who.int/csr/disease/avian_influenza/en/index.html.
- UN FAO: http://www.fao.org/ag/againfo/subjects/en/health/diseases-cards/special_avian.html.
- OIE: http://www.oie.int/eng/en_index.htm. Link to upcoming Paris Anti-avian influenza conference.
- US CDC: http://www.cdc.gov/flu/avian/index.htm.
- The US government’s web site for pandemic/avian flu: http://www.pandemicflu.gov/. New updates on the pandemic influenza blog and World Health Assembly’s influenza virus sharing resolutions.
- Health Canada: information on pandemic influenza: http://www.influenza.gc.ca/index_e.html. New travel Health Advisory: Avian Influenza A (H5N1) released.
- CIDRAP: http://www.cidrap.umn.edu/. Frequently updated news and journal articles.
- US Geological Survey, National Wildlife Health Center Avian Influenza Information: http://www.nwhc.usgs.gov/disease_information/avian_influenza/index.jsp. Updates from Hong Kong, Russia, and United Arab Emirates 1 Jun 2007.
(UN; WHO; FAO, OIE; CDC; Health Canada; CIDRAP; PAHO; USGS)

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2. Articles
Avian influenza A/(H7N2) outbreak in the United Kingdom
Editorial team (eurosurveillance@ecdc.europa.eu), Eurosurveillance editorial office http://www.eurosurveillance.org/ew/2007/070531.asp#2 (references removed)
“Several cases of influenza-like-illness (ILI) and/or conjunctivitis in humans have been linked to an outbreak of avian influenza in poultry at a smallholding near Corwen in northern Wales in the United Kingdom (UK). Three of the cases were hospitalized. H7N2, a low pathogenic strain of avian influenza (LPAI), has been identified as the cause of the poultry outbreak by the Department for Environment, Food and Rural Affairs (DEFRA). Four human cases (two in Wales and two in north-west England) have confirmed Influenza A infection and are closely linked in time and place to the discovery of the H7N2 avian influenza virus. Since there are currently very low levels of seasonal influenza in the UK, it is presumed that they are infected with influenza H7N2. Antiviral medication was given to three of the cases and all have now recovered. The poultry infections have been traced back to a public market selling poultry in Chelford, north-west England, on 7 May.

In accordance with UK policy, it was decided to offer antivirals to anyone who may have been exposed to the diseased poultry or had close contact with cases. By 30 May, 20 avian flu contacts had been identified who have or have had symptoms of an ILI or conjunctivitis. The National Public Health Service (NPHS) for Wales is using the following definitions of cases and contacts: A case is an individual with influenza-like illness (fever above 38° C, aches and pains, cough/head cold, sore throat or conjunctivitis) who has been in contact with affected premises or to known infected poultry (handling/within one metre) or close contact with another human case; A contact is defined as an individual who has been in contact with affected premises or with known infected poultry (handling/within one metre) or has had close contact with another person with confirmed or presumptive avian influenza.

The NPHS of Wales identified 256 people who might have had contact with the avian flu: in household settings, in a school and in the workplace setting, including patients and staff at two hospitals. Seventy-nine patients and staff from Ward 6 at Ysbyty Glan Clwyd have been offered antiviral medication as a precaution because of contact with a healthcare worker who became sick with an ILI and is a part of the outbreak. Sixty-nine patients and staff from the Accident and Emergency Unit, Trysfan Ward and Gogarth Ward at Ysbyty Gwynedd are also being contacted because a patient, who is now discharged, is being treated for the avian flu virus. As of 29 May, the NPHS had received microbiological test results from 12 patients in Wales. These were from swabs taken from the nose and throat and eyes. They were tested for the Influenza A viruses, including the H7 subtype that was isolated from the affected poultry. One test was positive for the H7 subtype and one for influenza A. Investigations are ongoing in the UK and further results and updates will become available through the web-sites of the relevant authorities - the Health Protection Agency (www.hpa.org.uk), DEFRA (www.defra.gov.uk), the Welsh Assembly Government (www.wales.gov.uk) and the NPHS for Wales (www.nphs.wales.nhs.uk).”

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Low Pathogenicity Avian Influenzas and human health
Influenza Team (influenza@ecdc.europa.eu); European Centre for Disease Prevention and Control http://www.eurosurveillance.org/ew/2007/070531.asp#3 (references removed)
“Human disease due to LPAIs Influenza A/H7N2 virus, as seen in the poultry outbreak described above, is one of many Low Pathogenicity Avian Influenzas (LPAIs). These have a genotype associated with causing milder symptoms in birds than the rarer high pathogenicity viruses and are negative on in vivo test. Outbreaks of LPAIs in birds, both wild and domestic poultry, occur regularly in Europe and are probably more common than recognised. Serological surveys of domestic poultry have found evidence of outbreaks that seem to have been missed. Occasionally, it seems that an LPAI transforms in birds to become a high pathogenicity avian influenza (HPAI) strain, but that is thought to be a rare event.

Human disease due to LPAIs The fact that an avian influenza is highly pathogenic for birds does not necessarily mean it is pathogenic for humans. However, one notable influenza (type A/H5N1) is both highly pathogenic for birds and humans. Influenza A/H7N2 virus infection in humans and all other human infections with LPAIs have only been associated with mild to moderate self-limiting disease, primarily conjunctivitis or flu like illness. Some cases have ended up requiring hospitalisation, but all have recovered. In addition, it is likely that there are asymptomatic infections and infections with mild symptoms that are never diagnosed because LPAI is not suspected and tested for. It is unclear whether or not there has ever been human-to-human transmission of an LPAI virus, although this has happened with some highly pathogenic viruses. During case-finding in outbreaks, people are often found to have symptoms compatible with LPAI infection, but turn out not to be infected. This was seen in an influenza A/H7N3 virus outbreak in the United Kingdom (UK) in 2006, when a single poultry worker presented with conjunctivitis and had confirmed infection, but others with similar symptoms were test-negative.

Who is at risk from LPAIs? Following requests from European Union (EU) Member States and the European Commission, the European Centre for Disease Prevention and Control (ECDC) is undertaking a formal risk assessment for avian influenza viruses (excluding H5N1) in relation to human health. We also posted a document examining this outbreak and its implications on our website on 28 May. After a thorough review of the literature, our assessment was that there is only limited public health risk from LPAIs, but that those who are at risk should nevertheless maintain vigilance and take precautions. The risk of infection with LPAIs is almost entirely confined to people who have close contact with domestic poultry (chickens, ducks etc) or their droppings. Human cases have almost entirely been in this category. People with small domestic and pet flocks are probably most at risk, as they are less likely to be able to take precautions than those working in industry and may be less aware of the dangers. Other groups that have occasionally been infected are veterinarians and people involved in controlling outbreaks in birds (culling) and people who work on industrial poultry farms. Most EU Member States have standard occupational guidance for the latter group, but there are others at theoretical risk who should follow basic precautions, as shown in the table below. However, no infections have been seen in these groups. For the vast majority of people, who have no direct contact with domestic birds or their droppings, the risk of acquiring LPAIs and the risk to health are almost non-existent. Human infection with LPAIs from wild birds has never been reported.

What actions should those with domestic poultry take? The advice from the ECDC has not changed and is the same as for reducing the risk of acquiring infection with HPAIs. People with small domestic flocks in Europe should always look out for ill-health in their birds and promptly report such to the authorities. They and their families should also maintain basic hygiene as this will minimise the risk of them catching LPAIs and the more dangerous pathogens that poultry may carry such as campylobacter and salmonellosis. The ECDC has produced model guidance on this for use by national authorities.

What is the risk of a pandemic resulting from an LPAI? Essentially this risk is unknown and unknowable. It is thought that each of the three pandemics of the 20th century had a link with avian influenza, as some avian genes seem to have appeared in the resulting human pandemic strain. Although there is particular concern about avian influenza H5N1 because of its high pathogenicity in humans and its stability over time in bird populations, there is no prima facie reason to imagine that the next pandemic strain will contain genes from a HPAI rather than an LPAI.”

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Transparent Development of the WHO Rapid Advice Guidelines
Holger J. Schünemann et al. PLoS Medicine Vol. 4, No. 5, e119 doi:10.1371/journal.pmed.0040119
Abstract: “Emerging health problems require rapid advice. We describe the development and pilot testing of a systematic, transparent approach used by the World Health Organization (WHO) to develop rapid advice guidelines in response to requests from member states confronted with uncertainty about the pharmacological management of avian influenza A (H5N1) virus infection. We first searched for systematic reviews of randomized trials of treatment and prevention of seasonal influenza and for non-trial evidence on H5N1 infection, including case reports and animal and in vitro studies. A panel of clinical experts, clinicians with experience in treating patients with H5N1, influenza researchers, and methodologists was convened for a two-day meeting. Panel members reviewed the evidence prior to the meeting and agreed on the process. It took one month to put together a team to prepare the evidence profiles (i.e., summaries of the evidence on important clinical and policy questions), and it took the team only five weeks to prepare and revise the evidence profiles and to prepare draft guidelines prior to the panel meeting. A draft manuscript for publication was prepared within 10 days following the panel meeting. Strengths of the process include its transparency and the short amount of time used to prepare these WHO guidelines. The process could be improved by shortening the time required to commission evidence profiles. Further development is needed to facilitate stakeholder involvement, and evaluate and ensure the guideline's usefulness.”
http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0040119

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Prophylactic and Therapeutic Efficacy of Human Monoclonal Antibodies against H5N1 Influenza
Cameron P. Simmons et al. PLoS Medicine Vol. 4, No. 5, e178 doi:10.1371/journal.pmed.0040178
Abstract: “Background New prophylactic and therapeutic strategies to combat human infections with highly pathogenic avian influenza (HPAI) H5N1 viruses are needed. We generated neutralizing anti-H5N1 human monoclonal antibodies (mAbs) and tested their efficacy for prophylaxis and therapy in a murine model of infection. Methods and Findings Using Epstein-Barr virus we immortalized memory B cells from Vietnamese adults who had recovered from infections with HPAI H5N1 viruses. Supernatants from B cell lines were screened in a virus neutralization assay. B cell lines secreting neutralizing antibodies were cloned and the mAbs purified. The cross-reactivity of these antibodies for different strains of H5N1 was tested in vitro by neutralization assays, and their prophylactic and therapeutic efficacy in vivo was tested in mice. In vitro, mAbs FLA3.14 and FLD20.19 neutralized both Clade I and Clade II H5N1 viruses, whilst FLA5.10 and FLD21.140 neutralized Clade I viruses only. In vivo, FLA3.14 and FLA5.10 conferred protection from lethality in mice challenged with A/Vietnam/1203/04 (H5N1) in a dose-dependent manner. mAb prophylaxis provided a statistically significant reduction in pulmonary virus titer, reduced associated inflammation in the lungs, and restricted extrapulmonary dissemination of the virus. Therapeutic doses of FLA3.14, FLA5.10, FLD20.19, and FLD21.140 provided robust protection from lethality at least up to 72 h postinfection with A/Vietnam/1203/04 (H5N1). mAbs FLA3.14, FLD21.140 and FLD20.19, but not FLA5.10, were also therapeutically active in vivo against the Clade II virus A/Indonesia/5/2005 (H5N1). Conclusions These studies provide proof of concept that fully human mAbs with neutralizing activity can be rapidly generated from the peripheral blood of convalescent patients and that these mAbs are effective for the prevention and treatment of H5N1 infection in a mouse model. A panel of neutralizing, cross-reactive mAbs might be useful for prophylaxis or adjunctive treatment of human cases of H5N1 influenza.”
http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0040178

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Immunogenicity and Safety of Intradermal Influenza Immunization at a Reduced Dose in Healthy Children
Susan S. Chiu et al. PEDIATRICS Vol. 119 No. 6 June 2007, pp. 1076-1082 (doi:10.1542/peds.2006-3176)
http://pediatrics.aappublications.org/cgi/content/abstract/119/6/1076
Abstract: “OBJECTIVES. We conducted this study to test the hypothesis that intradermal influenza vaccination at one fifth of a standard dose elicits comparable immunogenicity to full-dose intramuscular vaccination in children. PATIENTS AND METHODS. We conducted a randomized, open-label study in 112 healthy children aged 3 to <18 years to compare the immunogenicity and safety of intradermal vaccination at one fifth of a dose with standard intramuscular vaccination. Analyses of hemagglutination inhibition antibody titers to each antigen in each group included geometric mean titers before and 21 days after vaccination, fold increase in geometric mean titers after vaccination, seroprotection rate, and seroconversion rate. RESULTS. The mean age of the subjects was 10.11 ± 4.04 years in the intradermal vaccination group and 10.57 ± 3.91 years in the intramuscular group. Intradermal vaccination was safe. Induration and mild erythema at the injection site were reported at 25% and 57%, respectively, in the intradermal group. Fold increase of geometric mean titers against influenza A/Caledonia was robust in both groups (11.1-fold and 12.9-fold increase in the intramuscular and intradermal groups, respectively), whereas that for B/Shandong was more modest (4.3–4.4). Both approaches elicited very high geometric mean titers against influenza A/Panama: 1360.5 and 893.9 for the intramuscular and intradermal groups, respectively, but because the prevaccination antibody titers were high, the fold increase of geometric mean titers was only 4.5 and 2.6, respectively. CONCLUSION. The immunogenicity of one fifth of a dose of influenza vaccine delivered by the intradermal route is comparable to the standard-dose intramuscular vaccination in children as young as 3 years of age.”

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How can IT respond to a flu pandemic?
“Monday morning, 9 am. The CEO calls you into an executive meeting as word comes that a full-blown H5N1 avian influenza pandemic is spreading rapidly from central Asia. Your job: Keep mission-critical IT systems working despite staff absenteeism rates that could reach 40 per cent at the height of the pandemic, which is expected to run its course over a period of six to eight weeks. Supply chain disruptions are expected as countries close their borders, so you can’t count on spare parts. With emergency travel restrictions in effect, you can forget about moving staffers between global locations to cope with labor shortages. You also need to enable remote access for an unprecedented number of employees who will either be out sick, caring for ill family members or afraid to come to the office. You have weeks, possibly just days, before the outbreak overtakes one of your major data centers. Are you ready? For many businesses, the answer is probably no. . . .”

This article from Computerworld Malaysia discusses IT and pandemic influenza; it includes the following topics: LACK OF READINESS A NORM; UNCERTAIN OR OVERWHELMED?; IN THE HANDS OF TECHNOLOGY; ASIAN PRODUCTION HUBS; LIMITATIONS OF REMOTE ACCESS and; MANAGING SECURITY RISKS”
(Computer World June 2007)

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3. Notifications
CDC Guidelines for Large-Scale Influenza Vaccination Clinic Planning
To facilitate the most efficient and safe delivery of available vaccine via large community clinics, these recommendations and guidelines have been developed to assist with planning large-scale influenza vaccination clinics by public and private vaccination groups. Ideally, plans from private and public groups should be shared to identify best practices, avoid unnecessary overlapping of services, and maximize the effective and efficient delivery of influenza vaccinations.

This document provides general guidance to help ensure smooth operations at large-scale vaccination clinics under 8 major headings: Leadership roles; Human resource needs; Vaccination clinic location; Clinic lay-out and specifications; Crowd management outside of the clinic; Crowd management inside of the clinic; Clinic security; Clinic advertising.
(CDC 5/23/07 http://www.cdc.gov/flu/professionals/vaccination/vax_clinic.htm?s_cid=ccu052907_flu1_r_e )

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Pandemic Flu Leadership Blog: HHS forum, runs May 22-June 27
On June 13, Michael O. Leavitt, Secretary, U.S. Department of Health and Human Services, is convening a leadership forum on pandemic preparedness, which brings together highly influential leaders from the business, faith, civic and health care sectors to discuss how best to help Americans become more prepared for a possible influenza pandemic. The Department is hosting this five-week blog summit to expand this conversation as part of an ongoing effort by the Department to help Americans become more prepared.
http://blog.pandemicflu.gov/

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Guidance for Industry: Clinical Data Needed to Support the Licensure of Seasonal Inactivated Influenza Vaccines
From U.S. Food and Drug Administration:
Includes sections on: Traditional Approval of a BLA for a New Seasonal Inactivated Influenza Vaccine (Effectiveness; Additional Studies to Support the Effectiveness of the Vaccine in Populations Not Included in the Clinical Efficacy Study; Safety; Pediatrics); Accelerated Approval of a BLA for a New Seasonal Inactivated Influenza Vaccine (Effectiveness; Safety; Postmarketing Confirmatory Studies); Additional Considerations (Types of Influenza Vaccines; Clinical Lot Consistency; Adjuvanted Seasonal Inactivated Influenza Vaccines; Pediatric Research Equity Act; Postmarketing Evaluations).
http://www.fda.gov/cber/gdlns/trifluvac.htm

***For Pandemic Influenza, go to the following URL: http://www.fda.gov/cber/gdlns/panfluvac.htm. (Guidance for Industry: Clinical Data Needed to Support the Licensure of Pandemic Influenza Vaccines).

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Technical Meeting on Highly Pathogenic Avian Influenza and Human H5N1 Infection
During the International Partnership on Avian and Pandemic Influenza (IPAPI) Meeting held in Bamako 8 Dec 2006, the need was discussed for a technical meeting on to be scheduled prior to the Senior Officials Meeting Conference to be held in New Delhi. FAO-OIE-WHO in collaboration with UNICEF and UNSIC are co-organizing the Technical Meeting, to be held in Rome, 27-29 June 2007. Participants will be presented a summary of the current global epidemiologic situation of HPAI in poultry, and a risk assessment of human infection with the H5N1 virus. An assessment of the current risk of a pandemic of influenza and the state of preparedness of countries will also be presented. There will be an assessment of current strategies and practices as have been applied over the last three years for the control of HPAI in poultry and reduction of the associated risk of human infection.

A report will be prepared which will provide strategic guidance for the prevention and control of HPAI/H5NI in poultry and associated human infections, in the short, mid, and longer-term. The report, which will be circulated among the donor community and the participants of the New Delhi Conference, is expected to inform and drive high-level policy and decision-making.
(FAO http://www.fao.org/avianflu/en/conferences/june2007/index.html )

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 apecein@u.washington.edu