Vietnam: Thanh Hoa Province Has Poultry #H5N1

18/08/2012

The local epidemic is urgently

(VOV) - Thanh Hoa province has 3 districts appear flu and destroyed thousands of birds.

• A/H5N1 flu outbreak in humans threaten
• Avian influenza outbreaks in many places back

Morning of 18/8, Pham Van Can, Station Director Veterinary stations Sam Son (Thanh Hoa), said the province Sam Son town appeared avian influenza in Quang Cu.

As he should, bird flu appeared in the area from 24/7.Once detected, the authorities have taken samples for testing and the results were positive for the H5N1 avian influenza. Shortly thereafter, in Quang Cu has destroyed 301 birds.

Hau Loc district, avian influenza broke out in the United Loc Commune, Hoa Loc, Loc Thinh than one week now and has conducted more than 13,000 destroyed birds.

Currently, local services appear to have enhanced checkpoints 24/24h, not for trading transport poultry from local. /.

ETA:  The article below describes the 3 districts much better:

Excerpt:

(THO) - As reported by the Department of Agriculture and Rural Development (MARD), the province had appeared three outbreaks of avian influenza in three districts as Sam Son, Yen Dinh, Hau Loc.

Due to timely detect and actively implement measures to prevent and combat service should initially be controlled. However, the weather conditions complicated, small livestock, scattered flocks large sum on the other hand, the poultry in the province have not been vaccinated should bird flu risk a widespread outbreak is very high.

http://baothanhhoa.vn/vn/xa-hoi/n95864/Tang-cuong-cong-tac-phong,-chong-dich-cum-gia-cam

Vietnam: H5N1 in Nghia Hanh, Quang Ngai Province

08/17/2012

Nhan Dan Online-afternoon 17-8, District Veterinary Station Nghia Hanh (Quang Ngai) said it had destroyed 1,500 birds tested positive for the H5N1 virus.

Veterinary Station of Nghia Hanh District detect poultry disease in 2 farms of Ho Nhu Tuan, in areas Agreement Pho Nam, Hanh Trung and Nguyen Quy village in the province of Phu Nam, Hanh Minh, Nghia Hanh District. Nghia Hanh veterinary stations were directly taken 18 samples at 6 dead duck farms have sent the Regional Veterinary Center IV (Danang) test. The results showed that 6 of the 18 samples positive for the H5N1 flu virus.

Currently Nghia Hanh District directed the authorities to urgently localized outbreaks, spray disinfection, sterilization to limit disease spread on a large scale.

According to the Center for Preventive Medicine Quang Ngai, from the beginning of the year, the province has not happened to bird flu. This is the first case in Nghia Hanh appeared H5N1 flu in poultry must be destroyed, zoning objectives coincide, detoxify limited spread ...

Public at Last, H5N1 Study Offers Insight Into Virus's Possible Path to Pandemic

[This is an excerpt, dated back in June 2012 It is an excerpt describing the mutations used in the two studies by Kawaoka & Foucher, to become a Pandemic]

Science 22 June 2012:
Vol. 336 no. 6088 pp. 1494-1497
DOI: 10.1126/science.336.6088.1494

There's a key difference between the studies, however. Kawaoka created a hybrid virus: He took the gene for a viral protein called hemagglutinin from an avian H5N1 strain and stitched it together with seven other gene segments from the pandemic H1N1 virus that swept the world in 2009 and 2010, and which is already well-adapted to humans. From this starting point, it took just four mutations in the hemagglutinin gene to create a virus that could travel through the air from one infected ferret—a popular animal model for human infection—and infect another. But Kawaoka's hybrid has not yet been found in nature.

In contrast, “the strong point” of Fouchier's study, Cox says, is that it started out with an actual H5N1 virus isolated from a human victim in Indonesia. In an e-mail to Science, Kawaoka agreed that Fouchier's study addresses the most urgent question more directly. “Ron's data are very important,” he said.

Fouchier's team first inserted several mutations they knew might help the virus adapt for mammalian spread. One key target was the virus's receptor binding site, the area within the hemagglutinin molecule that makes first contact with the host cell; scientists already knew that two mutations there can make the virus prefer mammalian cells over bird cells. Another mutation, in the polymerase protein complex, allows the virus to replicate in the cool environment of the human upper respiratory tract rather than in bird intestines, the much warmer environment where it usually resides.

These initial mutations alone didn't do the trick, however, so Fouchier's team decided to try a time-honored method to encourage a pathogen to adapt to a new host: They passed the virus from ferret to ferret by directly inoculating uninfected animals with nasal samples from infected ones and repeated the procedure a total of 10 times. (In his Malta talk, Fouchier called this a “really stupid” approach, a phrase widely interpreted to mean he regretted it. In fact, he says, he just meant that the technique, called passaging, is a simple one compared to the sophistication of creating targeted mutations. The confusion may have stemmed in part from the fact that the Dutch word for “stupid” can also mean “simple.”)

The end result was a virus that could move through the air from one caged ferret to another right next to it; in a first experiment, the virus transmitted from cage to cage in three out of four instances.

Prior to publication, media reports suggested that airborne transmission required five mutations. The reality is more complex. Each of Fouchier's transmissible viruses had at least nine mutations, five of which were shared by all. This core quintet may be sufficient, the team writes, but the big question is whether one or more of the other changes also plays an important role, Peiris says.

Fouchier already knows part of the answer. Once his team achieved transmission in the summer of 2011, the researchers began additional experiments to identify the minimum set of mutations needed to make the virus airborne. But before those experiments were finished, they submitted their manuscript to Science, worrying that Kawaoka or other scientists might beat them to the punch. “Usually when you discover something important, somebody else is discovering it, too,” Fouchier says. (He was right: Kawaoka, who says he didn't know about Fouchier's work, had submitted his manuscript less than 2 weeks earlier.) Now, Fouchier declines to discuss the results from the additional experiments, which are on hold as a result of the moratorium.

The published paper shows that the core set of five mutations includes the three that the team introduced themselves and two more that arose during passaging. And the resemblance to what Kawaoka found is “quite remarkable,” says James Paulson, a glycobiologist at the Scripps Research Institute in San Diego, California. Both teams found that two mutations at the receptor binding site—one of them identical in the two studies—are important; both discovered an additional mutation that makes hemagglutinin lose a sugar group, which apparently helps make room for the mammalian host cell receptor. Kawaoka also found a mutation in the hemagglutinin's stalk that improves the virus's stability and compensates for the other mutations, Paulson says. “It's tempting to think” that one of Fouchier's mutations plays a similar role—although it's not in the stalk but in another area where three hemagglutinin molecules align to form a so-called trimer.

Cox says she's “surprised” that it didn't take more mutations. In a study with Paulson published online by Virology in November, her team also mutated the receptor-binding site, but they had to make several other changes—including slotting in a human-adapted version of another viral gene called neuraminidase—to get airborne transmission. That led the authors to conclude that the virus might require “extensive evolution” to become pandemic. Fouchier's paper upsets that reassuring notion.

Both papers will aid surveillance efforts because they suggest which genetic changes to look out for in H5N1, Peiris says. But they also point to a limitation: Several mutations can have the same effect on the virus. “It wouldn't be appropriate to focus just on these mutations,” Peiris says. “The virus has different ways to go from A to B.” More research is needed to discover how many ways, he says.

Indonesia: Yogyakarta On Health Alert 9 Days before Feast of Eid-al-Fitr

Flow monitoring in the province of Yogyakarta Mudik

August 15, 2012

Director General of Disease Control and Environmental Health (PP and PL), Ministry of Health, Prof. dr. Tjandra Yoga Aditama SpP (K), MARS, DTM & H, DTCE, review the current health care going home in Yogyakarta Special Province (DIY), Monday afternoon (13/8).

Prof. Tjandra activities started with a review of a health post at Adi Sutjipto Airport, Yogyakarta. Health services in these posts have been commenced in the nine days before the feast of Eid al-Fitr (H-9) or on August 10, 2012, handled by the Port Health Office (KKP) class IV DIY, assisted health center staff and the local Health Department.

-snip-

In addition, Prof. Tjandra Yoga is also reviewing the PKU Muhammadiyah Hospital of Yogyakarta, because it is one of the hospitals in the standby route. It is interesting, in this hospital there called an ambulance motorcycles, motorcycle is carrying medical equipment so that they can out of the village.

"Currently, the faculty of Medicine, University of Islam Indonesia (UII) in Yogyakarta is developing a form of motorcycle ambulances like this", said Prof. Tjandra.

[continued, click on title for full article]

Direct Comparison of an Inactivated Subvirion Influenza A Virus Subtype H5N1 Vaccine Administered by the Intradermal and Intramuscular Routes.

Abstract

Background. Direct comparisons of similar doses of a novel influenza virus antigen administered by the intradermal route and the intramuscular route have not been reported.Methods. A total of 227 healthy adults aged 18-49 years were randomized to receive 2 doses 1 month apart of a subvirion inactivated influenza A virus subtype H5N1 (rgA/Vietnam/1203/2004) vaccine containing 38.7 μg of H5N1 hemagglutinin (HA), by the intramuscular route or by the intradermal route using the Mantoux technique. Clinical and serologic responses were assessed.Results. Injection site reactions were more frequent in the intradermal group. Immune responses and the geometric mean titer of serum hemagglutination inhibition and neutralizing antibodies 1 month after receipt of the first dose were similar and low but were significantly higher after 2 doses of vaccine in both groups.Conclusions. Intramuscular and intradermal delivery of vaccine were both well tolerated. Immune responses after 2 doses of this influenza A/H5N1 HA (38.7 μg) were low and not significantly different when given by the intradermal or intramuscular route. Evaluation of higher dosages, alternative intradermal delivery methods, and the addition of adjuvants will be needed to enhance the immunogenicity of inactivated influenza A/H5N1 vaccines by the intradermal route.Clinical Trials Registration. NCT00439335.

PMID:

22891287

[PubMed - as supplied by publisher]

OIE: Avian Influenza H7N7 Found in Netherlands

NETHERLANDS - Low pathogenic avian influenza virus H7N7 has been discovered in the village of Hagestijn, the Netherlands.

The outbreak was reported to the OIE by Dr Christianne Bruschke, Chief Veterinary Officer, Ministry of Agriculture, Nature and Food Quality.

The outbreak occured on a free-range farm and was discovered during a routine check.

In total 31,870 free range laying hens were destroyed. The cause of the outbreak is unknown.

Poxviruses Deploy Genomic Accordions to Adapt Rapidly against Host Antiviral Defenses

SALT LAKE CITY – Scientists have discovered that poxviruses, which are responsible for smallpox and other diseases, can adapt to defeat different host antiviral defenses by quickly and temporarily producing multiple copies of a gene that helps the viruses to counter host immunity. This discovery provides new insight into the ability of large double-stranded DNA viruses to undergo rapid evolution despite their low mutation rates, according to a study published by University of Utah researchers in the Aug. 17, 2012, issue of Cell.

Poxviruses are a group of DNA-containing viruses that are responsible for a wide range of diseases in both humans and animals, including smallpox. Unlike smaller RNA-containing viruses, such as those that cause influenza and HIV, which are able to evade host immune responses through rapid mutation, poxviruses have larger genomes and low mutation rates and little is known about their adaptive strategies against host defenses.

"Poxviruses encode a variety of genes that help them to counter host immune defenses and promote infection," says Nels Elde, Ph.D., assistant professor of human genetics at the University of Utah School of Medicine and first author on the study. "Despite ample evidence that the poxvirus genome can undergo adaptive changes to overcome evolving host defenses, we still don't know that much about the mechanisms involved in that adaptation."

To determine mechanisms of adaptation, Elde and his colleagues studied the vaccinia virus, a type of poxvirus best known for its role as the vaccine used to eradicate smallpox. Previous research has shown that vaccinia virus encodes two genes, known as K3L and E3L, which inhibit host defenses that normally block viral infection. In this study, Elde and his colleagues started with a strain of vaccinia virus that had been altered to delete the E3L gene and repeatedly propagated this E3L-deficient strain in human cells to see how well the virus would replicate. They found that this E3L-deficient strain was quickly able to increase infectious virus production by selectively increasing the number of copies of the K3L gene in its genome.

"This highly specific and rapid gene amplification was unexpected," says Elde. "Our studies show that increasing K3L copy number leads to increased expression of K3L and enhanced viral replication, providing an immediate evolutionary advantage for those viruses that can quickly expand their genome."

Elde and his colleagues also found that, in addition to K3L copy number amplification, some of the E3L-deficient vaccinia strains also acquired a mutation consisting of a single amino acid substitution in the K3L gene. Both the mutation-bearing and multicopy K3L viruses displayed improved viral fitness, or ability to replicate in the host environment, compared to wild-type vaccinia virus. The emergence of this beneficial amino acid substitution suggests that increasing K3L copy number facilitated the appearance of the variant by providing additional mutational targets, despite the virus' otherwise low mutation rate.

"We were able to demonstrate at least two strategies by which poxviruses are able to adapt diverse mechanisms of host immunity," says Elde. "Our observations reveal that, while poxviruses do undergo gene mutation, their first response to a new, hostile host environment can be rapid gene expansion. We also found evidence that the virus genome can contract after acquiring an adaptive mutation, thus alleviating the potential trade-off of having a larger genome, while leaving a beneficial mutation in place."

Although smallpox was officially eradicated by the World Health Organization in 1980, concerns about the use of smallpox as a bioterrorism agent have spurred renewed interest in the study of vaccinia and other poxviruses. In addition, poxvirus infections, such as monkeypox, can be transmitted from animals to humans and the adaptive strategies of poxviruses may be relevant for other infectious organisms.

IDRI and Medicago Announce FDA Authorization to Initiate a Phase 1 Clinical Trial for an H5N1 Vaccine with GLA Adjuvant

Previous post today on this, located here

All Editing below is mine
Press Release
Seattle, WA | August 16, 2012

The Infectious Disease Research Institute (IDRI), a Seattle-based non-profit research organization that is a leading developer of adjuvants used in vaccines combating infectious disease, and Medicago Inc. (TSX: MDG; OTCQX: MDCGF), a biopharmaceutical company focused on developing highly effective and competitive vaccines based on proprietary manufacturing technologies and Virus-Like Particles (VLPs), announce that they have been cleared by the U.S. Food and Drug Administration (FDA) to initiate a Phase 1 clinical trial for an H5N1 Avian Influenza VLP vaccine candidate (“H5N1 vaccine”). This is an important step toward development of an influenza vaccine that could be rapidly and widely administered in case of a pandemic flu outbreak. The trial is focused on evaluating the safety and immunogenicity of the H5N1 vaccine, combined with IDRI’s Glucopyranosyl Lipid A (“GLA”) adjuvant, which will be administered intramuscularly or intradermally. Each study participant in the trial will receive two doses of a given formulation in order to collect and compare data. The trial is believed to be the first human test of an intradermal adjuvant – a technology platform that could potentially benefit a number of worldwide vaccination programs – and could result in a vaccine that could be self-administered in case of a pandemic. “A massive flu outbreak would cause a strain on health care centers as people rush to get a vaccination,” said Darrick Carter, Ph.D., Vice President of IDRI’s Adjuvant Technology program and co-principal investigator for the project. “Our idea is to ultimately produce a one-dose vaccine that you could give yourself – imagine a flu vaccine that you can easily administer using a simple, painless microneedle device arriving in your mailbox.”

"This research collaboration may provide for expedited vaccination and greater ease of use in the event of an influenza pandemic,” said Andy Sheldon, President and Chief Executive Officer of Medicago. "We view our collaboration with IDRI on this important initiative as a testament to the quality and efficacy of our H5N1 Influenza VLP vaccine. We look forward to now combining our vaccine candidate with IDRI’s adjuvant and the microneedle technology. Together, these three technologies could enhance protection, reduce the amount of product required, and simplify vaccine distribution and administration.”

According to the Centers for Disease Control and Prevention, the highly pathogenic avian influenza A (H5N1) virus is a deadly virus that occurs mainly in birds including domestic poultry. Though relatively rare, sporadic human infections with this virus have occurred and caused serious illness and death. Because of the unpredictability of pandemic flu, efforts are being made to create and stockpile a vaccine to combat H5N1 that reduces the amount of vaccine needed per person and can be easily administered.

“The predicted efficacy of a pandemic influenza vaccine is directly related to three key components: the nature of the vaccine, the way the vaccine is administered, and the presence or absence of a given adjuvant,” said Steven Reed, Ph.D., IDRI’s President, Founder and Chief Scientific Officer, and co-principal investigator for the project. “IDRI’s adjuvants can be used to increase the number of available vaccine doses by reducing the amount of vaccine needed per individual – this is called ‘dose sparing.’ Combining our adjuvant technology with Medicago’s rapid VLP technology is key to the next generation of flu vaccines, as well as an innovative delivery method from NanoPass. This gives us a great platform to test.”

The H5N1 vaccine candidate includes IDRI’s GLA adjuvant and is produced in Medicago’s plant-based expression system, which is speedier than the traditional route of producing flu vaccines in eggs. The adjuvant system has been successfully combined with Medicago’s vaccine candidate and other recombinant protein antigens to elicit both humoral and cell-mediated immune responses associated with protection in pathogenic animal challenge models. In animal studies, GLA has also been shown to expand the cross reactivity of antibodies induced by the H5N1 vaccine to other potential pandemic influenza strains such as H2N2.

The Phase 1 clinical trial is expected to start in September 2012, and will enroll 100 healthy adult volunteers, ages 18-49 years, at three locations in the U.S., testing for safety and immune response. The trial is anticipated to take 15 months to complete, and initial safety and immunology data are expected in the first quarter of 2013. It is funded by a multi-million dollar grant IDRI received from the Defense Advanced Research Projects Agency (DARPA), a division of the United States Department of Defense, to develop an influenza vaccine for pandemic flu.

While the trial will include testing of the traditional intramuscular route of delivery for comparison purposes, NanoPass’ proprietary MicronJet600™ microneedle device will test the intradermal route that could further improve immunogenicity. “Intradermal injection may have advantages over the intramuscular route in that the injection is painless, needle-free, and potentially more immunogenic as it provides targeted delivery of the vaccine to specialized cells of the immune system,” said Yotam Levin, M.D., Chief Executive Officer of NanoPass. "We have demonstrated in a recent Phase 2 study that we actually improve the immune response of seasonal flu vaccines in the elderly, despite using only 20% of the dose. This is an enabling technology that allows reducing the dose of antigens and/or adjuvants, improving the vaccination effect and at the same time improving patient comfort and compliance, making it an attractive proposition for pandemic preparedness.”

In June 2011, Medicago reported positive final results from its Phase 2 human clinical trial with its H5N1 vaccine with an alum adjuvant. Healthy volunteers in the Phase 2 trial received two doses 21 days apart, and data were analyzed 21 days after the last dose. The vaccine induced a solid immune response and was found to be safe and well-tolerated. The H5N1 vaccine has been tested in over 200 healthy volunteers to date, none of whom experienced any serious adverse reactions.

Vietnam: A/H5N1 flu outbreak in humans threatened

The article below talks about the new strain, how the poultry are healthy, show no signs of disease, and how the vaccine has been reduced in effectiveness by 35-40%. It also mentions that in Ha Tinh it has monitored more than 260 people that have had contact with poultry. I just added the province of Bac Kan, as having poultry infected with H5N1. Post below this one.

16/08/2012

Since early this year, the country has discovered four cases of influenza A/H5N1, including 2 deaths.


According to Nguyen Van Binh, Director of Preventive Health (MOH), the bird flu recurrence in some provinces such as Quang Binh and Ha Tinh and Hai Duong, Hai Phong and Ninh Binh is an increased risk of spread of influenza A/H5N1 in humans.

Ha Tinh is one of the local avian influenza occur is urgently implement preventive measures to infect humans.

Mr. Nguyen Luong Tam, Director of Preventive Health Center of Ha Tinh province, said the center is to monitor more than 260 cases in frequent contact with poultry. If you detect any cases of suspected influenza A/H5N1 expression will be treated immediately quarantined.

Since early this year, the country has discovered four cases of influenza A/H5N1, including 2 deaths. Recently notified the Department of Animal Health (Ministry of Agriculture and Rural Development) on the results of genetic analysis showed that explanation appears branch new bird flu virus in North, Central and Western Highlands. Time, the protective effect of vaccine before the new strain of bird flu this decrease, only 35-40%. This makes the risk of A/H5N1 flu in humans are higher.

Nguyen Tran Hien, Director of the Institute of Hygiene and Epidemiology, said direct contact with infected birds is the main route of transmission. The fact that time, most cases of influenza A/H5N1 were related to breeding, slaughtering and eating poultry.

But today is the most difficult job there is no circulating virus clinical signs in poultry flocks healthy, why people do not know how sick poultry as a precaution. This is also the most difficult to control pathogens and potential risk of transmission from poultry to humans, in which the elderly and children are the easiest most viral infections due to less resistance.

Besides, the new strain found in poultry excreta of a highly contagious disease spread through the air, dust and respiratory problems. Nguyen Tran Hien said: "First priority must be to prevent the spread of epidemics in poultry. Besides, the phenomenon must be detected early bird mortality and notify local authorities to promptly prevent epidemic. Absolutely not slaughter and use sick poultry. Health sector must work closely with the veterinary services, strengthening health education and propaganda for people to better understand the risk of transmission and outbreak of influenza in poultry and humans, warning people to enhance more measures of personal hygiene, food hygiene to prevent disease transmission from poultry to humans. "

Department of Preventive Medicine recommend the local health sector have bird flu as Quang Binh, Hai Duong, Ninh Binh and Ha Tinh, Quang Ninh quickly implement measures to prevent, not to bird flu chance to spread to humans, especially propaganda for people to understand the mechanism of transmission of disease. This time, though not yet detected any cases of new influenza A/H5N1 but people should not be subjective, by two A/H5N1 flu deaths were due earlier this year after nearly two years neglected no cases New.

Vietnam: #H5N1 in Bac Kan Province

Announcement of the avian influenza and blue ear pig
17:06 '16/08/2012 (GMT +7)
Currently, the province had appeared avian influenza H5N1 in Cho Don district and swine blue ear (PRRS) in Cho Moi District. Under these circumstances the PPC has officially announced the epidemic.
By decisions dated 15/08/2012 1248/QD-UBND province on the publication the avian influenza (H5N1) epidemic areas shall include: Bang Lung town, Cho Don epidemic areas under threat include the social : Yen Thuong commune, Ban Thi Ngoc Phai, Bang Lang, Luong Bang, The List, By Phuc, the table. Buffer includes the communes of Binh Trung Nghia Ta, East Vienna, the sequence, the same Lac.
For publication on the blue ear pig, PPC has decided on 16/8/2012 1263/QD-UBND, which includes social service areas: Agriculture House, Agriculture Thinh Cho Moi district. Epidemic-threatened areas include: Cao Ky, Thanh Mai, Thanh Binh. Buffer included in the remaining of Cho Moi district.
PPC for professional bodies and local service organizations to implement immediately the preventive measures in accordance with the provisions of the Ordinance on Veterinary Medicine and the current regulations.

Vietnam: Farmers brace for bird flu

HANOI, 16 August 2012 (IRIN) - Farmers in north and central Vietnam are bracing for a new wave of bird flu outbreaks as local authorities are urged to take precautions against the disease.

In the past two weeks, local news reported around 67,000 poultry infected with the H5N1 virus in the northern city of Hai Phong, and 17,000 in Ha Tinh Province in the centre of the country. This follows six outbreaks in late July in the north that led to almost 30,000 birds being culled, according to figures reported to the Organization for Animal Health (OIE).
-snip-
Four people are reported to have died from the disease this year - the first cases in 21 months. According to the World Health Organization, there have been 121 confirmed human H5N1 infections and 61 deaths in Vietnam since the virus first appeared in the country in 2003.

[click on title for full article]

Human H5N1 Vaccine Trial

8/16/2012 4:16 AM ET
(RTTNews) - The Infectious Disease Research Institute or IDRI, a Seattle-based non-profit research organization, and Medicago Inc. (MDG.TO:Quote,MDCGF.PK) announce that they have been cleared by the U.S. Food and Drug Administration or FDA to initiate a Phase 1 clinical trial for an H5N1 Avian Influenza Virus-Like Particles vaccine candidate or "H5N1 vaccine".

The IDRI said that the trial is focused on evaluating the safety and immunogenicity of the H5N1 vaccine, combined with IDRI's Glucopyranosyl Lipid A or "GLA" adjuvant, which will be administered intramuscularly or intradermally. Each study participant in the trial will receive two doses of a given formulation in order to collect and compare data.

The H5N1 vaccine candidate includes IDRI's GLA adjuvant and is produced in Medicago's plant-based expression system, which is speedier than the traditional route of producing flu vaccines in eggs.

The IDRI said it expects that the Phase 1 clinical trial will start in September 2012, and will enroll 100 healthy adult volunteers, ages 18-49 years, at three locations in the U.S., testing for safety and immune response. The trial is anticipated to take 15 months to complete, and initial safety and immunology data are expected in the first quarter of 2013.

[continued - click on title for full article]

Mexico: AH7N3 Bird Flu Update

Previously posted here, excerpt:

August 8, 2012

Avian Flu Campaign: 80M Birds Vaccinated in Mexico
Published August 15, 2012
Eight million chickens have been slaughtered in Mexico and another 66 million have been vaccinated in an ongoing effort to contain a bird flu outbreak that began in June in the western state of Jalisco.

A total of 80 million birds have been vaccinated against the AH7N3 avian flu virus in Mexico, where another 8 million birds have been destroyed, federal health officials said.
Inspections have now been conducted at 426 poultry farms in the Los Altos region of the western state of Jalisco during the 7-week-old emergency health campaign, the National Food Health, Safety and Quality Service, or Senasica, said.
Inspectors found 385 farms to be free of the virus, while 41 farms tested positive for the presence of the AH7N3 avian flu virus, the Senasica said.
"The farms free of the virus have been allowed to move their products to the main markets," Senasica director Enrique Sanchez said.
A quarantine remains in effect in the high-risk area, with the transportation of poultry products restricted to prevent the spread of the virus.
Officials have also ordered the slaughter of birds that test positive for the AH7N3 virus, the Senasica said.
A total of 11,253 samples from farms in 20 states have been tested, yielding negative results and "giving us scientific evidence to support the idea that the outbreak has been contained for now in the Los Altos zone of Jalisco, where it originated," Sanchez said.
Avian flu does not pose a danger to people consuming meat or eggs, and the measures being taken are designed to protect poultry production, Sanchez said.
An analysis of the vaccination campaign will be released in the next few days and officials will reveal the next steps to be taken, the Senasica said.
Mexican health officials said in late June that the presence of the avian influenza virus had been detected in Jalisco and took emergency measures to prevent its spread.
The vaccine is being produced by the National Veterinary Biological Production Agency, or Pronabive, with assistance from three private pharmaceutical companies.
Mexico, according to National Poultry Producers Association figures, produces nearly 2.5 million tons of eggs and 1.2 million tons of meat annually.

H5N1 vaccine trial shows low immune response, regardless of delivery

CIDRAP 8/13/12
A subvirion inactivated H5N1 avian flu vaccine produced a weak immune response after two high-antigen doses, regardless of whether volunteers received the vaccine intramuscularly (IM, or standard injection) or intradermally (ID) via the Mantoux technique. US researchers immunized 227 adults 18 to 49 years old with a Sanofi Pasteur H5N1 vaccine that was produced using methods similar to those used to manufacture Fluzone, a seasonal flu vaccine. The volunteers were randomly chosen to receive two doses 28 days apart either IM or ID. Although the vaccine contained 38.7 micrograms (mcg) of antigen (compared with 7.5 mcg for each of the three strains in Fluzone), immune responses were low: Only 25.4% in the IM group and 23.0% in the ID group achieved a fourfold or greater increase in antibody titer (measured by hemagglutination inhibition) 28 days after the first dose, and those percentages climbed to only 35.4% and 42.5%, respectively, after 56 days. Both delivery methods were well tolerated. The authors conclude, "Evaluation of higher dosages, alternative intradermal delivery methods, and the addition of adjuvants will be needed to enhance the immunogenicity of inactivated influenza A/H5N1 vaccines by the intradermal route."
Aug 13 J Infect Dis abstract

Bird flu claims 9th victim this year in Indonesia

Fox News
August 13, 2012


JAKARTA, Indonesia – The Health Ministry says bird flu has killed a 37-year-old man in central Indonesia, marking the country's ninth fatality this year.

The Ministry's website said Monday that the man died July 30 in Yogyakarta province after being hospitalized for five days.

It confirmed that the man who lived near a chicken slaughterhouse was infected with the H5N1 virus after apparently coming into contact with sick birds.

The virus, which began ravaging poultry across Asia in 2003, remains entrenched in Indonesia. Experts fear it could mutate into a form that passes easily among people, potentially sparking a pandemic. But most human cases have been linked to contact with sick birds.

The World Health Organization says 359 people have died from it worldwide. Indonesia remains the hardest-hit country, accounting for 159 deaths.

Vietnam: Prevent bird flu #H5N1

8/11/12

According to the Veterinary Department, after a lull, bird flu has now reappeared and tend to spread in a number of localities in the Red River Delta region and North Central. Preliminary statistics, more than 100 thousand birds were killed and forced destruction in the locality.

Experts warned that the coming months, the risk of an outbreak on a large scale is very large due to the weather complex with the transformation of strains of influenza virus A (H5N1) exist in the environment.Meanwhile, in the northern provinces, effective bird flu vaccine has decreased significantly (only about 60% protection level), more poultry vaccination has not been prescribed vaccines. Status of poultry smuggling continues.

While the blue ear disease has not been completely extinguished, the bird flu reappeared is a matter of great concern to the livestock industry as well as public health by high virulence of influenza virus A (H5N1) . However, in fact, every occurrence of an outbreak of cattle, poultry outbreaks and localities are often passive, confused in implementing measures to prevent and combat. Many places loose control, quarantine, transport and slaughter of poultry, poultry products, as well as not attach importance to the monitoring, early detection of outbreaks for timely implementation of uniform measures against ... service delays caused, prolonged, causing great losses to farmers and the state budget. That's not to mention a few places to keep it secret services, delays in providing information and reports to the National Steering Committee to coordinate the overall implementation capacity stamping out measures.

To prevent bird flu effectively, the need to increase local autonomy, concentrating all forces and means fierce siege, extinguish the epidemic. In particular, enhanced surveillance for early detection, establish checkpoints block the transport of poultry and poultry products outside the outbreak and set up the inspection team and direct prevention services to village level and hamlets in the high-risk areas. At the same time, strengthen widely disseminating the right of people to understand the epidemic, voluntary cooperation with the authorities epidemic. In addition, increasing the role and responsibilities of the competent authorities in the implementation of policies to support people to expand and poultry development.

Notably, at this time, smuggled poultry situation still "hot" in the northern border province. It is thus important to the new and actively coordinate the relevant departments such as police, market management, agriculture and rural development and local government levels to eradicate even the line smuggled poultry.

Vietnam: Health Services of the provinces to strengthen monitoring

08/12/2012

Health staff redundant staff of local veterinary closely monitor bird flu.

According to the Veterinary Department of Hai Phong, far, bird flu broke out in 18 households, in 9 communes, 5 districts / counties, An Lao, Vinh Bao, Kien Thuy, Kien An, Yang Kinh.Tong increments took sick, death and destruction of the Hai Phong area up to 68,250 ducks. Mr. Phan Trong Khanh, Director of Hai Phong Department of Health said in the first year in implementing the guidelines of the Ministry of Health and City People's Committee, plans to prevent bird flu has been the health centers and hospitals proactive planning, budget, training for health workers and local supervision. Currently, the health sector has directed medical communes in the districts in the area affected by bird flu, in collaboration with veterinary staff to master the dead bird, mobilizing people and actively report provide leaflets to hand people, warned of the dangers of bird flu spreads to humans.

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Form a team of shock include anti-militia service, youth, veterinary, medical, police, to spray environmental disinfection or destruction of infected poultry, live at the checkpoints . Communal People's Committees are responsible to direct the adjacent commune health situation.

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Study: Children, middle-aged most vulnerable to variant H3N2

CIDRAP: Robert Roos * News Editor

Aug 10, 2012 (CIDRAP News) – A serologic study from Canada suggests that children and middle-aged adults have little or no immunity to the swine-origin variant H3N2 influenza virus (H3N2v), but about half of adolescents and young adults have some degree of immunity as measured by antibody levels.

The researchers also found that seasonal flu vaccines used in the past two seasons did not improve participants' ability to mount an immune response to H3N2v. Their report was published this week in the Journal of Infectious Diseases.

Given the results, "A specific vaccine would be needed in the event A(H3N2)v establishes epidemic spread," says the study, which was led by Danuta M. Sowronski, MD, of the British Columbia Centre for Disease Control as first author.

The H3N2v strain, which contains the matrix gene from the 2009 H1N1 virus, emerged last summer in the United States, causing a dozen cases. But more than 150 cases of H3N2v illness have been reported in the past few weeks, most of them in children who had contact with pigs, often at county fairs. The illnesses have generally been mild and self-limiting.

A flu expert with the US Centers for Disease Control and Prevention (CDC) said today that the new findings generally agree with those of previous studies by the CDC and others, but the finding of low antibody levels in middle-aged adults emerged more clearly in the new study than in previous ones.

The CDC has prepared a candidate vaccine for the novel virus, and clinical trials are expected this fall.

Samples from all ages
The Canadian researchers looked for cross-reactive antibodies to H3N2v, using 1,116 serum samples that had been collected in 2010 from people across the age spectrum. In addition, they tested sera collected from children and adults before and after receipt of the 2010-11 seasonal flu vaccine and from elderly people before and after receipt of the 2011-12 vaccine.

Hemagglutination inhibition (HI) and, in a subset of cases, microneutralization were used to assess antibodies to H3N2v.

Overall, 25% of the 1,116 participants had an HI antibody titer of at least 40 to the H3N2v strain, the level that's believed to confer some degree of protection. But no children younger than 5 years and fewer than 20% of subjects 14 or younger or over age 40 had this seroprotective level of antibody.

Between the ages of 14 and 40, half of the subjects had a seroprotective level of antibody to the virus, the report says. The proportion peaked at about 60% in adults in their 20s but dropped to about one-third for those in their 30s. Fewer than 10% of those between ages 40 and 69 and about 20% of those older than 69 had seroprotection.

The researchers also looked at cross-reactivity to an H3N2 strain called A/Sydney, which circulated in the late 1990s and was the most closely related and readily available human ancestor strain to H3N2v. Overall, they found a seroprotective level of antibody to A/Sydney in 61% of their samples. More than 90% of teens and adults in their 20s had seroprotection, and for adults overall the prevalence was more than 60%.

To test whether seasonal flu vaccine enhanced protection against H3N2v, the team looked for at least a fourfold increase in antibodies to the novel virus (seroconversion) after vaccination. They found that seroconversion rates were less than 15% in all age and vaccine groups, with little difference by age-group.

Among elderly people who received the 2011-12 seasonal vaccine, 72 received a vaccine containing the MF59 adjuvant. The researchers said the adjuvanted vaccine didn't enhance response to H3N2v compared with the other formulations.

"Our serologic findings suggest substantial protection against A(H3N2)v in late adolescence and young adulthood, but broad susceptibility in children and older adults," the authors say in summary.

The lack of protective antibody levels in middle-aged and older adults contrasts oddly with the fact that there was only one adult among the first 13 H3N2v cases identified, the authors comment. They say this "may reflect limitations in surveillance sensitivity, exposure opportunities or pediatric versus adult hygiene or other protective measures."

The explanation for the age-related variation in seroprotection may have to do with differences in the H3N2 strains that different age-groups were exposed to in childhood, the researchers suggest. They say that the A/Sydney strain circulated a few years after, and is 96.4% similar to, H3N2v's closest human ancestor, A/Wuhan.

Those who were children in the 1990s may have been "primed" by exposure to H3N2v ancestor strains, resulting in robust memory responses to related strains in later years, they write.

The authors note several limitations of their data and say the findings need confirmation elsewhere.

A CDC expert, Jacqueline Katz, PhD, said the Canadian findings generally agree with previous smaller studies conducted by her agency and a group in Norway. But she said the study is much larger and offers greater insight into the age-related differences in seroprotection against H3N2v. Katz is chief of the immunology and pathogenesis branch of the CDC's Influenza Division.

"Overall, the three studies agree that there is negligible cross-reactive antibody to the H3N2v virus detected in younger children," Katz said. The work also confirms previous findings that seasonal trivalent flu vaccine containing an H3N2 strain does not trigger much of a cross-reactive response to the novel virus, she added.

"What's novel about Skowronski's study is it's the largest to date and had the ability to look more closely at different age groups," she said. "They have quite an interesting finding that middle-aged adults, ages 40 to 69, show a substantial reduction in the level of cross-reactive antibody compared with younger adults."

The Norwegian study had a similar finding, but in a tighter age-group of adults, she said, adding that further research is warranted to try to find an explanation for the phenomenon.

Katz concurred with the Canadian team's suggestion that different childhood exposures may be a reason for the age-related differences in seroprotection.

"It may be that that particular group [middle-aged adults] had a different exposure, that they saw an earlier H3N2 virus for the first time, and didn't have the same robustness of response to the viruses from the 1990s that are closest to the H3N2v strain," she said. "We're interested in looking into that a little more."

"When you do genetic and antigenic analysis, you can see that viruses from the early 1990s are genetically most closely related to the hemagglutinin of the H3N2 variant viruses," Katz said. "So it does make sense that individuals who were of an age to be exposed to those in the early 1990s and made a robust response may have the highest cross-reactive antibody response to the variant strain."

Skowronski D, Janjua NZ, De Serres G, et al. Cross-reactive and vaccine-induced antibody to emerging swine influenza A(H3N2)v. J Infect Dis 2012 (Early online publication) [Full text] [Abstract]