It has been my own personal project to follow H5N1 for the last 3 years simply because it interests me. Attracted to this type of information like a magnet, I've been watching this relatively new influenza virus to see where it will go, how it will change itself, and possibly change our world. I have followed its country by country outbreaks, and watched for the important viral mutations such drug resistance or changes that allowed it to more specifically target mammals.
Keeping in mind at all times that we will be cleared impacted as HCW, as well as being members of our communities, and having families of our own to care for, I wanted to start the new year by opening a single focused pandemic thread that would also look at what we are doing nationally to prepare for a future pandemic. Is this the virus to spark the next pandemic? No one can answer that question. We can look back at the past to the last few pandemics, and in particular to the most devastating one in 1918, and extrapolate useful information about them, but we can not predict the future. We can only make comparisons with our situation now, and learn what worked to lessen morbidity and mortality in those past events. And, we can look at those other viruses, and compare them with what we are seeing now. For example, H5N1 is a Type A virus. We know that all pandemics are caused by Type A viruses. It is also an avian virus. The deadly 1918 virus, H1N1 was also an avian virus.
For this thread, as in the previous threads, I will be making use of news sources, scientific studies, govt bulletins such as the MMR, as well as flu forums and blogs devoted to this subject for my sources. Because press information, particularly the foreign press, is not always available for later access when I am looking back to check recent historical information, the use of these blogs and forums are important because archived information quoting the media and all other sources is always fully and easily available there with no worries about information disappearing or no longer being available. They also fully document their sources or I would not be using them.
With this link from Avian Flu Diary, a well researched source that I highly recommend, we can read the words of outgoing HHS Secretary Leavitt on our state of preparedness. Leavitt has done an admirable job during his tenure, but admits that there is much left to do.
A scant 33 months ago, I sent my first message about a race that HHS had just begun. As I said then, it was a race against a fast-moving virulent virus with the potential to cause an influenza pandemic. Since then, we have mobilized experts and resources across the country and around the world. I now send you this final message, as I look back at the unprecedented progress we have made in energizing a national pandemic influenza preparedness movement in those 33 months.
Today, many people mistakenly think influenza pandemics are a thing of the past, but influenza has struck hard in the era of modern medicine – much harder than most people realize. And it will strike again. Pandemics are hard things to talk about. When one discusses them in advance, it sounds alarmist. After a pandemic starts, no matter how much preparation has been done, it will be inadequate.
The three-year old Vietnamese boy from Southwestern province Dong Thap of Vietnam confirmed of being infected H5N1 virus died, a local doctor from the Ho Chi Minh Hospital of Tropical Diseases told Xinhua Thursday.
The infected patient named Tran Cong Phuc died this afternoon because of severe breathing difficulty caused by H5N1 virus tested by the hospital, said the doctor.
The fact that this 38 yr old woman seems to be doing well is good news. This is also a reason for concern as explained in the Recombinomics link.
For the 4th time this month (and the 8th time this year), Egypt is reporting a new H5N1 infection - this time in a 38 year-old woman from Asyut province.
This makes Egypt's 59th confirmed infection from bird flu since the virus arrived in that country in 2006.
... the recent mild cases raise concerns that the level of H5N1 cases in Egypt is markedly higher than reported. Many cases who do not develop pneumonia and have mild cases similar to the most recent case likely do not seek medical attention, while others may be treated for seasonal flu and recover untested for H5N1. Moreover, all seven confirmed cases in Egypt this year, prior to the most recent case were 1 ½ to 2 ½ years old. The confirmation of this number of toddlers, also suggests that there are more cases in older children and adults.
These mild cases in Egypt also raise concerns that the level of H5N1 in countries which report high case fatality rates, like Indonesia, Vietnam, and China also have a high number of mild cases that are untested or test negative, especially on samples collected after the start of Tamiflu treatment.
Dr. Niman over at Recombinomics has given some further elaboration on why these mild cases of bird flu occurring in Egypt are something to be alarmed about. This is a valuable link with some serious points being made.
H1N1 is one of the commonly occurring seasonal influenzas. It is now almost 100% resistant worldwide to one of our very few available antiviral drugs, Tamiflu.
H274Y is a genetic marker signaling that a virus has developed Tamiflu resistance. Flu viruses can and do exchange these pieces of genetic information like H274Y frequently. If it is in the best interest of the virus's survival to do so then there is increased pressure for this to happen. Acquiring Tamiflu resistance would be a very good thing for the bird flu virus, indeed. There have been some human cases where Tamiflu resistance has occurred that we know about, but thankfully it has been very rare. Widespread resistance to Tamiflu in the bird flu virus, H5N1 could be a very dangerous situation for humans.
The possibility of increased human to human transmission of bird flu that may be occurring with these milder cases is also something to be concerned about.
None of the eight confirmed cases in 2009 in Egypt have died. Only one was in critical condition. The other seven had a mild course. Milder H5N1 likely leads to more exposure of others, because the patient is not immediately hospitalized and isolated. The increased exposure would not only increase the likelihood of infecting others, but would also increase the likelihood of a second infection with H1N1 seasonal flu, which is almost exclusively Tamiflu resistant.
Tamiflu treatment of a patient co-infected with H5N1 and H1N1 carrying H274Y would apply pressure toward the transfer of H274Y from the H1 on H1N1 to the H1 on H5N1, either via reassortment or recombination. In seasonal flu, both transfers have been reported, raising concerns of similar exchanges between H1N1 and H5N1.
H274Y has been reported to have been independently introduced onto three H1N1 sub-clades that have been recently circulating. Moreover, the level of H274Y in the most widely circulating sub-clade (clade 2B - Brisbane/59) has increased to levels approaching 100%.
Thus, the high levels of H274Y in H1N1, coupled with increased circulation of H5N1 in human populations in Egypt raises serious concerns about the emergence of Tamiflu resistant H5N1 that is more efficiently transmitted in human populations.
Another mild case reported in Egypt today if this patient is indeed in stable condition as reported. I am afraid that Dr. Niman may be correct. The fact that these cases are mild does mean something, and that what it means is not good even though I am glad that most of these people have recovered. See post previous to this one for what the concern about mild cases is.
An Egyptian girl has been infected with the Bird Flu virus, bringing the number of these cases in the country to 60.
A spokesman of the Health Ministry said on Thursday Israa Abdel Shafi, aged two years and six months, was hospitalized in the province of Qina in southern Egypt.
The girl suffered from high fever and coughing after she mingled with dead birds suspected of bearing the virus. Her condition was described as stable after she given the required medications.
This would be the 10th case reported since January 2009 in Egypt. Most of these cases have been benign, and are occurring in toddlers again pointing to the possibility that actual cases of H5N1 are being missed and underreported in other age groups. Parents are likely to worry about bird flu, and take a sick baby to the doctor but an adult with the same symptoms is not going to a doctor unless seriously ill. The concern is that meanwhile the virus is making itself at home in humans undetected, and adapting to transmit more efficiently to that host.
A two-year-old Egyptian boy has contracted the highly pathogenic bird flu virus, bringing to 61 the number of confirmed cases in the most populous Arab country, state news agency MENA said on Wednesday.
The boy, from the province of Beheira in northern Egypt, was believed to have contracted the H5N1 virus after coming into contact with infected birds, MENA quoted health ministry spokesman Abdel Rahman Shahine as saying.
The boy was taken to hospital on Monday after he came down with a high fever while visiting extended family in another province. He was being treated with the antiviral drug Tamiflu.
I keep wondering why pigs are being raised in predominantly Muslim countries such as Indonesia and Egypt, but apparently they are for some reason. At any rate, the fact that pigs are being infected with H5N1 is not unexpected considering that the virus is endemic in those countries. This could be a cause for concern as this study explains.
Scientists report that H5N1 avian influenza viruses may be adapting to pigs, as evidenced by the finding that H5N1 viruses isolated from pigs in Indonesia were less harmful to mice than were H5N1 viruses from chickens.
The finding suggests that in growing in pigs, the virus may have become less harmful to mammals in general, the authors report. That sounds reassuring, but the authors say it may mean the virus is one step closer to turning into a human pandemic strain.
In the study, scientists from Japan and Indonesia collected viruses from chickens and pigs in Indonesia, grew them in laboratory cell cultures, and used them to infect mice. They found that the viruses from pigs were less lethal to mice than the viruses from chickens, according to their recent report in the Archives of Virology.
"We found that swine isolates were less virulent to mice than avian isolates, suggesting that the viruses became attenuated during their replication in pigs," the report states.
Pigs are seen as a possible intermediate host that can help avian flu viruses adapt to humans, because the epithelial cells in pigs' trachea can be infected by both avian and human flu viruses, the article notes. If avian and human viruses infected a pig at the same time, they could mix or reassort, giving rise to a novel strain that might be able to spread in humans. The flu pandemics of 1957-58 and 1968-69 were caused by avian-human hybrid viruses, though it is not known if they arose in pigs.
But even if they don't mix with human strains, avian flu viruses that infect pigs are believed capable of adapting to them--gaining the capability to grow efficiently in swine cells--and thereby adapting to other mammals, the authors write. Humans occasionally are infected with swine flu viruses, something that has been reported at least twice this flu season in the United States, according to the Centers for Disease Control and Prevention.
So far, H5N1 infections in pigs have been reported rarely or gone unnoticed because infected pigs show no signs of illness, the scientists write. But the authors, who include Chairul Nidom of Airlangga University in Surabaya, Indonesia, report that they found H5N1 infections in pigs in Indonesia in 2005, 2006, and 2007. They determined that the swine viruses were closely related to viruses in chickens found nearby, indicating H5N1 spread from chickens to pigs at least three different times.
The authors offer this interpretation of their findings: "Since our swine strains were isolated from pigs with no apparent influenza-like symptoms, the decrease of pathogenicity in mice suggests that the H5N1 viruses may have lost their pathogenicity in mammals during replication in pigs. Given that for the H5N1 viruses to cause a pandemic, they would likely become attenuated in humans, becoming attenuated in mammals may be a prelude to the generation of a pandemic strain."
Mostly, I do not post about the many suspected cases of bird flu that have been occurring in Indonesia. I read about them almost weekly, but I don't post them here because there is no way to verify the information since the Indonesian govt censorship began. They seem to be selectively notifying the WHO when they feel like it. The local press in that country keeps on reporting suspected cases, and those stories are not published in English but must be translated. This is being done on a daily basis by volunteers on the flu forums dedicated to this type of information, however this report was translated by the Bird Flu Information Corner weblog. They are a joint endeavor between Kobe University, Japan and the Institute of Tropical Disease, Airlangga University, Indonesia. The story of interest confirms the death of a toddler occurring last week, and says that his family members are showing symptoms. The local govt has declared that this is an area under "exceptional status".
When many people are at risk, the policy has been to give everyone Tamiflu prophylaxis, the so called "Tamiflu Blanket" although it appears that this time they are just giving it out to those with a fever. Tamiflu has been very effective thus far in halting the spread of the virus in local populations. Lots and lots of Tamiflu is being used, but it is the only antiviral being used, and for that reason someday there is a going to be a problem. How long will it keep on working? Obviously, not forever, but that is another story...
After the confirmed death of a toddler (Wahyu) last week, and amid reports that some family members are now suffering from fever, authorities have announced that the boy's neighborhood is now under KLB (Exceptional Status) for bird flu.
KLB in Indonesia basically refers to a heightened public health alert.
It appears that the area is being closely monitored, Tamiflu is being dispensed to anyone with fever, and that testing is underway among Wahyu's family and neighbors.
A change has been unfolding in the dynamics of avian influenza in Egypt. The most recent victims have overwhelmingly been toddlers and, these cases are mostly mild. Why is that? H5N1 is giving up virulence to get what in exchange? Is this temporary?
One of the axioms that is often repeated about novel influenza viruses is that for one to achieve pandemic potential, it has to attenuate. That means it has to become milder because doing so allows the virus to infect more hosts. Killing off all of the hosts does not make for a good survival strategy.
If this virologist is correct, the H5N1 virus has also become more efficient at human to human transmission. He suggests that looking for neutralizing antibodies in the former at risk groups would provide important information about the real spread of the disease. For example, they might start testing young women that have been raising poultry to ascertain if they have developed these antibodies. Many of the early cases in Egypt were young women.
The large number of cases suggests that the transmission to humans is more efficient, and mild cases are more likely to spread silently. Mild cases will be more likely to be diagnosed as seasonal flu, and those without a known link to poultry are unlikely to be tested. Moreover, the absence of pneumonia in almost all confirmed cases suggests that many other cases would resolve without Tamiflu treatment.
The mild cases in the spring of 2009 have similarities to cases in the spring of 2007, although the target population has changed. In the spring of 2007 the case fatality rate was also close to zero (16/17 survived), but most of the cases were children. That outbreak raised concerns that there were many additional children that were H5N1 infected, but not tested. Milder cases spread more easily because infected hosts remain active longer, increasing the number of exposed contacts, especially when the target population is school aged.
Recovery in the older age groups would lead to protective immunity, which would lower then number of confirmed cases in those age groups. These prior infections would funnel the infections into younger patients who had not been previously exposed.
The 10 fold jump in toddler cases this year raises concerns that undetected cases are also 10 fold higher than prior outbreaks, signaling a major spread of H5N1 in the human population.
The explosion of cases in toddlers demands a more aggressive testing of toddlers that do not have poultry contact. Similarly, an aggressive testing program of former at risk groups for detectable levels of neutralizing antibodies is long overdue.
More thoughtful insights from Dr. Niman on the possible significance of the mild cases of H5N1, bird flu that have been occurring recently in Egypt almost exclusively in toddlers.
The H1N1 virus referred to is a common, ordinary seasonal influenza virus. That virus is almost 100% resistant to the antiviral drug, Tamiflu. Seasonal flu viruses are very easily transmitted from human to human.
H274Y is a single nucleotide polymorphism, abbreviated SNP (pronounced "snip"). If a flu virus contains this SNP, it is Tamiflu resistant.
CFR refers to the case fatality ratio, the ratio of deaths within a designated population over a period of time.
Tamiflu is the drug of choice for treating bird flu, H5N1.
The commentary makes note of mild cases of H5N1 that occurred in Egypt in 2007, and that there may have been many more cases not recognized as H5N1 in children at that time.
The cases in 2007 raised concerns that the number of cases was markedly higher than the confirmed cases because they could easily be misdiagnosed as seasonal flu, and like seasonal flu, could resolve with or without medical attention or anti-virals. Thus, many of the children would recover and not be tested because a seasonal flu etiology would be assumed. Moreover, the children could spread the H5N1 to playmates or classmates, which would produce protective immunity in this population.
Protective immunity in children would help explain why the mild cases this year are almost exclusively in toddlers. The toddlers either were not born, or were infants in the summer of 2007, which would limit exposure. This year, they would be more active and more likely to come into contact with H5N1. Confirmed cases would be limited to this age group because the prior at risk groups would have some level of immunity, which would keep viral loads below detection limits.
In addition, the high number of toddler cases would signal a more efficient spread of the virus to humans, which may be linked to prior silent spreading in individuals who had developed some protective immunity.
The silent spread could have significant consequences. H1N1 has now become Tamiflu resistant, so co-infections involving H1N1 and H5N1 could lead to H274Y jumping to H5N1, conferring resistance. Similarly, increased spread in human hosts could make transmission more efficient due to H5N1 picking up additional changes from H1N1.
Moreover, the milder, efficiently spread, Tamiflu resistant H5N1 could recombine with more virulent H5N1 to increase virulence, similar to the high CFR in Egypt between the two milder outbreaks, as well as infections preceding the milder cases in the spring of 2007.
Therefore, aggressive testing of toddlers who have no clear link to poultry is necessary, as is aggressive screening of prior at risk groups for detectable H5N1 antibodies, such as children in southern and central Egypt who accounted for the vast majority of confirmed cases in the spring of 2007.
The silent spread of H5N1 in human populations sets the stage for increased transmission efficiencies and a serious, if not catastrophic, pandemic.
...the last two Egyptian bird flu cases, both toddlers, lived in houses adjacent to each other.
Undoubtedly, investigation over the route of infection is ongoing.
The fact that these two cases are from neighboring houses does not necessarily imply human-to-human transmission. They could have shared a common infectious source, such as backyard chickens.
This child is older at age 6. He is also much more sick.
A six-year-old boy has contracted bird flu, the 63rd recorded case since the first outbreak of the disease in Egypt in 2006 and the third in a week, the health ministry announced on Sunday.
Ali Mahmud Ali from Shubra al-Khaimah, north of Cairo, was hospitalised on March 28 in the Egyptian capital, ministry spokesman Abdel Rahman Shahin said, as cited by state news agency MENA. The diagnosis came after about a week, he said.
The child is in a serious condition and is being treated with frontline anti-flu drug Tamiflu, Shahin added.
While most of the reports on the H5N1 virus in this thread are of human cases in the hot zone countries like Indonesia, Egypt, and China, the virus is present elsewhere sometimes in unexpected places.
Japan
10 raccoons discovered with bird flu antibodies
There have been reports all along of infected carnivorous mammals in the countries where H5N1 has occurred either in wild birds or poultry. It was so common in Indonesia for cats to be infected that reportedly there was a word for the sound that dying cats would make as they fell out of the trees.
The Japanese have identified raccoons as a possible risk factor for bringing the virus into poultry farms.
These animals were most likely to have been descended from raccoons that escaped from zoos or had been pets at one time. These are North American mammals that are not native to Japan. The article points out that they had likely picked up the virus by eating dead birds that had been infected with H5N1 or were born to parents that did.
Ten wild raccoons have been found with signs of previous H5N1 bird flu infections, according to a joint study by Tokyo University and Yamaguchi University.
This is the first time mammals in this country have been found with bird flu virus antibodies, which develop as a result of infection. Before the discovery, only birds had been found with bird flu antibodies.
The research team, which presented a paper on its findings at a conference of the Japanese Society of Veterinary Science in Utsunomiya on Saturday, warned that infected raccoons could introduce the virus into chicken farms and noted that countermeasures were needed.
It is believed that the H5N1 strain of the bird flu virus is highly likely to mutate into a new type of influenza. In Japan, there have previously been reports of domestic chickens, wild whooper swans, jungle crows and mountain hawk-eagles infected with the virus.
The research team collected and examined blood from 988 raccoons captured since 2005 at three locations in western Japan and one location in eastern Japan. In the blood of 10 raccoons from three of the locations, the team found antibodies that had developed after past H5N1 infections. In two of the three places, not even birds had been found with the antibodies before this time.
Bavaria
As this translation indicates, H5N1 is still present in wild birds in Europe. This is not so worrisome unless poultry become infected which does happen sometimes for example when geese or ducks are on water adjacent to poultry farms.
As the reader observed, it's rare for WHO to scoop the hot-zone media. The report:
The Ministry of Health in Viet Nam has reported a new confirmed case of human infection with the H5N1 avian influenza virus. The case has been confirmed at the National Institute of Hygiene and Epidemiology (NIHE).
The case is a 3 year old boy from Chau Thanh District, Dong Thap Province. He developed symptoms on 12 March, was hospitalized on 13 March, and died on 19 March.
WHO concerned about possible bird flu human carriers in Egypt
Dr. Niman of Recombinomics has been posting about the change in the demographics of bird flu infection in Egypt. Not everyone agrees with Niman's views, but his arguments do get noticed. Apparently now even the WHO finally has become concerned about what the changes could mean, and an investigation is being launched. If only they would permit the US Naval Lab, NAMRU 3 to release the data on the recent H5N1 sequences. Since NAMRU 3 became a WHO affiliated laboratory, they have been withholding data that they used to release freely to other virologists. Not good...
Whether such cases exist still has to be put to the test and will be the focus of a planned Egyptian government study backed by the global health body, said John Jabbour, a Cairo-based emerging diseases specialist at WHO.
The emergence of symptomless human carriers of the virus would be a worrisome development because it could allow the virus, undetected and untreated, more time to mutate inside the human body, Jabbour said.
"If there is any sub clinical case in Egypt, the aim is to treat immediately to stop the reproduction of the virus. Because whether (through) mutation or reassortment, this will lead to the pandemic strain," he said.
Of the 11 Egyptians infected with bird flu this year, all but two have been children under age three while adult cases have all but dried up. All have survived.
That is starkly different from the same period a year ago, when seven people -- mostly adults and older children -- contracted the virus and three died.
Jabbour said the rise in infections in children without similar cases among adults had triggered questions as to whether adults were being infected with the virus but not falling ill.
"There is something strange happening in Egypt. Why in children now and not in adults?" he said. "We need to see if there are sub clinical cases in the community."
Jabbour said there had been no known instances of sub clinical bird flu cases in humans in other countries where the disease was present. Some birds, like ducks, are known to carry and spread the virus without showing symptoms, he said.
The Egyptian study, which Jabbour said should begin in the coming months, would test the blood of people who may have been in contact with infected birds but had not become sick.
The cytokine storm is allegedly what kills the victims of H5N1, and what killed millions in the 1918 influenza pandemic. The Reveres have tried to simply an explanation of a recent study on how the overreaction of the victims own immune systems ends up killing the patients. The explanation is a little technical, but not overly so, and can be understood by most with an interest in the subject.
There is so little that can be done for the hapless victims that the possibility of using the diabetic drug, Avandia is intriguing.
Generally when posting from Effect Measure, I lift the entire article with permission so as not to post the comments out of concern for possible TOS violations. Not to worry this time as most of the comments following this article are from some very savvy folks that are worth a read as well.
It is becoming increasingly clear that some of the nastiest effects of virulent flu strains like the 1918 H1N1 or the bird flu H5N1 are related to the violent and uncontrolled immediate response of the immune system, a response which destroys lung tissue by runaway inflammation. Helpless clinicians have tried to damp down the immune response in bird flu patients by using steroids which depress all parts of the immune system. It hasn't worked. The immune system is a very complex apparatus with many moving parts. Those parts have to be coordinated and regulated. Using steroids is like laying off the police force. It isn't going to protect people from attacks from pathogens like the flu virus. The intricate choreography of the immune system, like the cruder one of a police response, is based on signaling and communication between its different parts. Most of that signaling is done by chemical messengers called chemokines. When one kind of immune cell is ready to recruit others to help, it releases a chemical signal. When that signal is received (by another chemical, called a receptor), it activates a new set of biological events. And so on. I'd love to lay out the whole intricate system for you, but I can't. No one can. At the moment it's like a giant jig saw puzzle where we know some of the pieces and how they fit together, but not always where they sit in the Big Picture and there are lots of pieces still lying in the puzzle box. But we are making progress and the PNAS paper by Aldridge et al. is a step to putting some more in place.
The Editors of Effect Measure are senior public health scientists and practitioners. Paul Revere was a member of the first local Board of Health in the United States (Boston, 1799). The Editors sign their posts "Revere" to recognize the public service of a professional forerunner better known for other things.
indigo girl
5,173 Posts
Vietnam confirms 3rd human case died of bird flu this year
http://news.xinhuanet.com/english/2009-03/19/content_11036655.htm
Egypt Reports 59th Human H5N1 Infection
http://afludiary.blogspot.com/2009/03/egypt-reports-59th-human-h5n1-infection.html
The fact that this 38 yr old woman seems to be doing well is good news. This is also a reason for concern as explained in the Recombinomics link.
http://www.recombinomics.com/News/03190902/H5N1_Egypt_Mild_09.html