Take our pop quiz to find out how knowledgeable you are regarding bird flu

Developments in 2007

Many flu experts think that it is only a question of time as to when a bird flu pandemic will start, although we stress this view is far from universal. For a sampling of opinions, visit Wikipedia.

Compared to late 2005 and 2006, 2007 saw fewer outbreaks among birds (wild and domestic) and humans as far as infection is concerned. However a steady trickle of cases in Indonesia persists, largely because of poor domestic bird management (i.e., chickens). The good news is that none of these outbreaks look like clusters involving human-to human transmission. The bad news is that with the bird migratory season in full swing outbreaks are again occurring, with some notable cases in turkey farms in the UK. In addition, as flu season has gotten underway toward the end of 2007, several new human cases have appeared in China, Mynamar, and Pakistan. It remains to be seen whether this uptick in both human cases and avian infections will be sustained and lead to further outbreaks.

More clades continue to develop. (Clades are like families of subtypes within a given strain.) This is to be expected. What still concerns us is that PCR (polymerase chain reaction) testing of isolates from human and avian sources, particularly in Asia are still showing poor matches in many cases. What that means is that humans are not being infected by chickens or other birds directly; they are being infected by other sources of H5N1. We presume these are mammalian, but this is not proven. Nevetheless, H5N1 has the widest range as far as infection of mammals is concerned, compared to other influenza strains. All of this means we are still not out of the woods yet, but does demonstrate that has been hard for the H5N1 variants to become pandemic-capable, which experts think only involves 1-2 mutations in the HA gene.

Another area of concern is the mortality rate. In Indonesia during the summer of 2006, this was close to 75% and shows no sign of abatement. In some epidemics, as the transmissibility of a virus increases, there can be a decrease in the mortality rate, but we do not know whether this would be the case with H5N1. There are a number of factors that are responsible for the high virulence, including the "doubling" of the cleavage site in the HA subunit, mutations in the NS gene, and the E627K polymorph in the PB2 gene, which was first seen in the Quinghai strain originating in China.

The use of the neuraminidase antiviral oseltamivir (Tamiflu) has also been disappointing. It is becoming clearer that in severe cases of avian influenza, if this drug is not given within 48 hours of infection, it is only marginally useful. While we don't know the exact reason for this, it is thought that the virus quickly induces a cytokine imbalance in the cell--known also has a cytokine storm or hypercytokinemia--that creates havoc within the affected cells. Webster’s group in Memphis, TN, however, (Salomon et al., 2007) has challenged this theory.

Pandemic Avian or Bird Flu Preparedness

We have researched the scientific literature and studied reports of the H5N1 avian flu strain and concluded that few health organizations are truly prepared for a flu pandemic, or for that matter, major outbreaks of any infectious pathogens. Surveys of US physicians also agree with that statement. Reports of the SARS (Severe Acquired Respiratory Syndrome) epidemic, in Toronto, Canada, showed that several health workers died as a result of treating infected patients before measures that could have controlled the spread of the infection were implemented on a timely basis. Arguments have been put forth to suggest that this was because the WHO gave little or no warning of the SARS epidemic originating in China. However, this does not obviate the need to be prepared at all times. If a flu pandemic does break out, it is quite possible that the WHO might not be able to give much warning either.

The bottom line is that you cannot successfully treat patients during an epidemic, unless your health center has measures in place to prevent the spread of infection. And that's just the beginning. Triage and ring prophylaxis procedures must also be ready to go. Reconfiguration of rooms and units must occur. Supplies must be in place. And finally, your staff members must be trained and understand what will be required of them. How can all of this be accomplished in such a short space of time?

We have a pilot biopreparedness project that involves a series of surveys, protocols, procedures, and training modules that can be adapted to any health facility so that it can operate under pandemic conditions, whether it is H5N1 flu or another infectious disease. Our protocols, which are designated Stages I, II, and III, to match the severity and phases of a flu pandemic, can be implemented in a matter of weeks and are based upon hard lessons learned over many years by health facilities involved in the outbreaks of infectious diseases. They involve the key concepts of isolation unit configurations, infection control, personal protective equipment (PPE), triage, and ring prophylaxis. We hope to be demonstrating this pilot concept in health care facilities in the state of Wyoming in 2008.

How knowledgeable are you about avian flu? Try taking the test below. A few of these statements are taken from newspapers; others are quotes from "experts." After reading each question, ask yourself whether the statement is accurate or not and compare your response to the answers. Be careful: one or two questions are trick questions.

Ten Questions to Test Your Avian Flu Knowledge

Question 1: No one can contract avian flu from a person infected with avian flu because it migrates to the lungs and it is very difficult for a patient to cough up the virus into the air.

Question 2: N95 masks offer complete protection from a person infected with pandemic avian flu when used in conjunction with appropriate gloves, gowns, and polycarbonate face shields.

Question 3: When a short course of oseltamivir (Tamiflu) (75 mg twice daily for 5 days) is given to a patient infected with avian flu, it will enable the patient to recover, provided it is given with 48 hours of initial infection.

Question 4: The only way the H5N1 strain can evolve into a pandemic strain is by acquiring key polymorphisms in the HA subunit that will enable better binding efficiency to a cell membrane's receptors.

Question 5: Pandemic strains of flu acquire genetic changes primarily via the mechanism of point mutation--i.e., a change in a single nucleotide.

Question 6: A pandemic is spread by only one subunit strain (genovar) of influenza A.

Question 7: In a severe flu pandemic, two or more million fatalities could result in the USA.

Question 8: The use of corticosteroids is helpful in treating a patient with avian flu.

Question 9: Radiology is one of several diagnostic criteria that should be used to identify which patients have avian flu during a flu pandemic.

Question 10: The H5N1 virus can only survive for a few hours on an indoor surface.

Answers to Avian Flu Questions

Question 1: Not true. We have observed a number of avian flu cases in which limited human-to-human transmission probably occurred. In January, in Turkey, for example, there were two large clusters in which transmission occurred between parents and children, and between siblings. In some of the Turkish cases, the polymorphism S227N was found. S227N alters the affinity of the HA subunit to bind to both sialic acid alpha-2,6-galactoside receptors located in the nasopharygeal epithelial cells, in addition to the sialic acid alpha-2,3-galactoside receptors located in the alveolar cells (Gambaryan et al, Virology, 2006;344:432-8). The finding that SA alpha-2,3-galactoside receptors existed in alveolar cells (the preference for current wild type avian H5N1 flu strains) was not known until recently (Shinya et al, Nature 2006;440:436-6); van Riel et al, Science 2006, March 23). Moreover, analysis of the clusters that occurred in 2006 in Indonesia cannot rule out limited human-to-human transmission (Kandun et al, 2006).

Question 2: Not true. N95 masks offer significantly more protection over no facial protection (Seto et al, 2003). However, they will not block everything. This is due to leaks around the mask, even when properly fitted, as well as the fact that the filter can only trap larger droplets containing flu virus. Since the virus is much smaller than 1 micron, this can pass through the filter, a situation likely to occur in true airborne transmission. Although true airborne transmission might be overall a minor mechanism, it can still occur, particularly when aerosolizing operations are conducted with a patient harboring a pandemic flu strain (e.g. Hui et al., 2006. In addition, the mechanism in "superspreaders" might involve airborne transmission.

Question 3: Not always true. In 2005, there was a cluster of cases in Vietnam in which several patients given oseltamivir died as result of a mutation that arose--H274Y. This mutation, which had been seen before in lab, animal, and human situations, confers resistance to the drug and unlike most mutations, has proved to be viable. (See de Jong et al, New England Journal Medicine, 2005;353:2667-72.) As a result, recommendations to double the length of treatment, with perhaps higher initial dosages, have been discussed. (Moscona, New England Journal Medicine, 2005;353:2633-2636; Hayden et al, Antiviral Therapy 2005;10:873-7).

Question 4: True. The wild type H5N1 strains in circulation must acquire polymorphisms that enable increased binding efficiency to the sialic acid alpha-2,3-galactoside receptors. This will enable the kind of human-to-human transmission efficiency necessary for a pandemic strain.

Question 5: Not true. Despite this oft-quoted statement, it is far more likely that the H5N1 strain will acquire key polymorphisms through genetic reassortment or recombination from genes present in other flu strains, such as H1N1 or H1N2 in pigs (WHO, Emerging Infectious Diseases, 2005;11:1515-1521; Recombinomics Commentary, March 23, 2006). It is also possible that other mammalian reservoirs might exist through which recombination or assortment events could occur.

Question 6: Not true. Analysis of human isolates, from the 1918 pandemic H1N1 flu strains, showed at least two predominant circulating genovars (Reid et al, Emerging Infectious Diseases 2003;9:1249-53). Interestingly a number of H5N1 clades have developed from which might spring two more pandemic H5N1 subtypes (WHO, Emerging Infectious Diseases, 2005;11:1515-1521). A recent paper by Mills et al, (PloS Medicine 3:e135) also suggests that the introduction of multiple subtypes increases the risk of a pandemic, and makes it harder to "contain" an outbreak.

Question 7: True. Numerous epidemiological studies have shown that a figure of 2 million deaths in the USA is likely during a severe pandemic. This figure could be higher if collateral deaths from denial of health care occur for at-risk groups for a number of diseases, such as type I diabetics, or transplant patients.

Question 8: Probably not true, although the jury's still out on this one. The use of corticosteroids has been tried in patients infected with avian H5N1 strains, and was widely used in the recent SARS (Severe Acquired Respiratory Syndrome) outbreak. The idea behind this treatment is to mitigate the hypercytokinemia often observed--the so-called cytokine storm (Chan et al, Respiratory Research, 2005;6:135), but immunomodulators, such as methylprednisolone have not always been successful (Yuen and Wong, Hong Kong Medical Journal 2005;11:189-99). Part of the problem may be inappropriate dosages. Probably the best treatments are those we have seen for SARS cited in an article written by So, Lau, and Yam and which could be easily adapted to H5N1 treatment. We reviewed the situation recently in avian influenza, and came to the conclusion that clinicians should first establish whether a true adrenal insufficiency exists in the patient, otherwise treatment with corticosteroids should not be attempted (Carter MJ, J Med Microbiol, 2007).

Question 9: True. Radiology of the lungs can be of help in determining the stage of the disease, (and in the monitoring of treatment) but the problem is that a patient infected with a pandemic flu strain is extremely infectious. How does one prevent the patient from spreading the virus during transfer to the radiology department and the taking of X-rays? Protocols need to be developed to control infection.

Question 10: Not true. Flu viruses can easily survive for 24-48 hours on hard surfaces (Bean et al, Journal Infectious Diseases, 1982;146:47-51), although they do not survive as long on soft surfaces and only a few minutes on human skin.

Pandemic Flu Preparedness Services Offered

If you would like to know more about our avian flu pandemic preparedness services, please contact us. We can offer a one-hour PowerPoint presentation on-site as part of our initial consultation, as well as on-site preparedness surveys, the results of which are presented in a report. In addition, we have protocols that can be modified based on the results of the survey and translated into short procedures manuals. Staff training sessions are also an option.