Announcement

**Laidback Al** · October 17, 2011, 11:24 PM

Re: How Dangerous is Bird Flu (H5N1) to Global Public Health? Part 2

Indonesia is starting to heat up

On October 10th, WHO confirmed the death of the 179th individual from West Jakarta (island of Java) to be infected with H5N1 in Indonesia.

Since then three family members, a mother, a son, and daughter, have died in Bangli Regency on the island of Bali, each suspected with bird flu.
see: http://www.flutrackers.com/forum/sho...d.php?t=174971

Elsewhere in Bali, an individual from the Tabanan Regency is hospitalized with a suspected H5N1 infection.
see: http://www.flutrackers.com/forum/sho...d.php?t=174992

And another suspected H5N1 case from Klungkung Regency in Bali has also been reported.
see: http://www.flutrackers.com/forum/sho...d.php?t=174812

And on Lombok island, the island directly to the east of Bali, there are five individuals that have been hospitalized or treated for symptoms of bird flu. Although several of these individuals are from the same village none as yet seem to represent a cluster.
see: http://www.flutrackers.com/forum/sho...d.php?t=174951

So far, with the exception of the family cluster in Bangli Regency, none of these cases seem to be a result of human-to-human transmission. As always, the concern of any novel infectious disease is human-to-human transmission. The 10 recent and currently suspected H5N1 cases in Bali and Lombok need detailed scrutiny, both locally and internationally.

**sharon sanders** · October 19, 2011, 10:29 AM

Re: How Dangerous is Bird Flu (H5N1) to Global Public Health? Part 2

Today's updated situation in Indonesia as of this posting time:

Current Suspected Bird Flu Cases

Indonesia, Bali, Bangli, Jehem village, Tembuku district: mother of the siblings, who died on October 9 in Bali, has also died after presenting with symptoms of bird flu.

Indonesia, Bali, Bangli, Sekardadi village, Kintamani district: 4-year-old bird flu suspect Sekardadi, Subdistrict Kintamani, transferred to Sanglah Hospital

Indonesia - Bali, Denpasar :Sanglah hospital treats bird flu supect from Tabanan

Indonesia - Bali, Klungkung: New suspected bird flu patient from Kusamba, Dawan district, in Klungkung Regency hospital

Indonesia, Lombok Island: 5 Suspected cases of bird flu hospitalized 4 test negative in initial test.

Indonesia, West Java - Bird flu suspect in Cianjur Hospital

* WHO confirmed
+ Indonesia MOH confirmed

**Laidback Al** · October 26, 2011, 12:02 AM

Re: How Dangerous is Bird Flu (H5N1) to Global Public Health? Part 2

Indonesia H5N1 Update - Family Cluster

Today, the Ministry of Health in Indonesia has officially reported the infection and death from H5N1 of a brother and sister in Bali and reported those cases to WHO under IHR (link). We can expect that these two cases will be posted by WHO in the next day or two.

As noted in this thread, the mother of the two children also died perhaps from H5N1.

Elsewhere I discuss this cluster. . .

Originally posted by Laidback Al View Post

New Family Cluster of H5N1 cases in Bali in Indonesia

A family cluster of H5N1 of a mother and two children is being reported from Bali in Indonesia (link). The mother is a suspected case and is being treated while both of her children died from locally confirmed H5N1.

If these three cases are confirmed by WHO, it would be a significant announcement for Indonesia. Although family clusters of H5N1 infection in various countries are not rare, many of the infected family members, even if they die, are never confirmed. The largest cluster of H5N1 cases in Indonesia to date is the Karo cluster with seven confirmed cases in 2006 (timeline link). The largest H5N1 family cluster in Indonesia after the Karo cluster is the Hendriansyah family from Lampung, Sumatra, in 2005 (link 1, link 2, link 3) with three WHO confirmed cases.

The current outbreaks of three locally confirmed and suspected H5N1 human cases in Bali and the two separate suspected cases from the adjoining island of Lombok (link) need to be carefully monitored for human-to-human transmission.

Indonesia H5N1 Update - Vaccination and Virus Evolution

H5N1 is enzootic in Indonesia as evidenced by widespread outbreaks in poultry throughout the country. Indonesia has chosen to fight H5N1 in poultry through a vaccination program, mostly unsuccessful. In the study linked below, the authors found that H5N1 poultry vaccination in Egypt and Indonesia seems to be causing the H5N1 strains to be evolving.

Link: Evidence for differing evolutionary dynamics of A/H5N1 viruses among countries applying or not applying avian influenza vaccination in poultry

Indonesia (and elsewhere) H5N1 Update - Multiple Strains

This past week WHO published an article on the various known clades of H5N1. This information has been distilled and explained by Mike Coston in this link. Since 1996 H5N1 has exploded into multiple separately identifiable strains.

Summary

Multiple strains of H5N1 are circulating in the world today, some because of unsuccessful poultry vaccination programs in various countries. Vaccine research is not keeping up with these evolving strains. And the now confirmed family cluster of two died children (and probably the mother as well) reminds us of how ill prepared the world is if one of these H5N1 strains becomes an easily transmissible pandemic virus.

**Laidback Al** · October 30, 2011, 11:49 PM

Re: How Dangerous is Bird Flu (H5N1) to Global Public Health? Part 2

KLB for human H5N1 in Bali?

KLB is an acronym for Kejadian Luar Biasa translated from Bahasa Indonesia as an "extraordinary event" (see link). A KLB event generally refers to a disease outbreak requiring special attention by public health officials in Indonesia.

Today, in a news article, Bali's Chief Medical Officer explains that a KLB for human H5N1 has not been announced presumably because it would affect the tourist industry in Bali and affect the livelihood of local farms dependent on raising chickens.

We don't know what the threshold of confirmed human H5N1 cases is in Indonesia for a KLB. Two children have already died from confirmed H5N1 infections in Bali in the past several weeks.

The fact that a H5N1 KLB is even being discussed and dismissed to the media means that the world needs to be even more diligent in monitoring suspected cases of H5N1 in Bali and surrounding islands.

**Laidback Al** · December 2, 2011, 01:28 PM

Re: How Dangerous is Bird Flu (H5N1) to Global Public Health? Part 2

Will Bird Flu Spread Easily Among Humans?

Recently, there has been a lot of media coverage about experiments with bird flu (H5N1) and ferrets in the Netherlands (see this FluTrackers thread). Ferrets are often used for influenza testing because they are a good proxy species for influenza infection and transmission among humans. Researchers working with H5N1 viruses found that after several generations of infections among ferrets, the virus was easily transmitted between animals.

As noted in the FluTrackers thread, many of the media reports have focused on ethical issues such as tinkering with a known virulent influenza strain, maintaining a virulent strain with the potential for a laboratory escape, and whether details of the experiment should be published because of fears of bioterrorism. While these issues need to be debated by the bioethicists, we need to consider the actual results of the laboratory research.

That laboratory research demonstrates the viability of an easily transmissible virulent strain of H5N1 after a serial passage of 10 generations in the ferrets. These experiments are ample proof that H5N1 has the potential to become a pandemic virus strain probably without the help of human intervention. If we can extrapolate from the Netherlands study, all it would take is a unbroken chain of H2H transmission of 10 steps or generations for the virus to reassort into a transmissible virulent H5N1 pandemic virus.

Taken together the Netherlands experiment and other research noted in the CIDRAP article present a very clear picture. H5N1 has the potential to transmit easily between humans and become a pandemic virus. We can no longer just hope that H5N1 reassortment will not happen in the wild, we must be prepared for it.

**Giuseppe** · December 2, 2011, 03:20 PM

Re: How Dangerous is Bird Flu (H5N1) to Global Public Health? Part 2

H5N1 is really a menace for humans because of its panzootic spread among the most overcrowded places in the world, ie China, Egypt, Indonesia, India.

On the other hand, H5N1 is constantly in contacts with humans and other mammals (wild or domestic, such as cats, dogs, horses, pigs) since its emersion in large scale in 2003 (and perhaps even earlier in 1997).

How many copies of H5N1 virus were around in such longer time-lapse?

Among this immense viral cloud, how many viable for human-to-human transmission viruses emerged?

What is the barrier - if any exists - between a readily transmissible virus and a short or dead-end chain of cases?

Every minute H5N1 enters in contact with animals (birds and mammals) and copies its RNA exploring all possible combinations to survive hosts immune response.

We are facing a huge gap in our knowledge of these pathogens but perhaps we should investigate this strange behaviour of a virus that survives in a multitude of hosts but continues to be 'restricted' to humans.

Is the host the problem?

I would like to not wait that a civil unrest in Egypt will reveal to us the real extent of this possible host restricted virus capabilities.

**Laidback Al** · December 7, 2011, 03:45 PM

Re: How Dangerous is Bird Flu (H5N1) to Global Public Health? Part 2

Virology Blog

In the FT thread Man Made H5N1 -Super Version, Gert has posted excerpts from Vincent Racaniello's Virology Blog where he comments on the latest H5N1 transmission study among ferrets. The full blog can be found here.

Dr. Racaniello's blog does an excellent job of undermining the media hype surrounding the threat of a laboratory created H5N1 "super" strain. He notes that there is no certainty that the laboratory virus could transmit between humans or even retain its virulence.

Buried within his discussion is an important nugget of truth that we all need to consider in relation to emerging infectious diseases.

"Nature is far better at producing viruses that can kill"

The laboratory experiments of Nature could have far more lethal consequences than ferret experiments in the Netherlands. That is why public health surveillance is so critical. Continuous scrutiny and real time monitoring of Mother Nature's experiments are where we should be concentrating our efforts.

**Giuseppe** · December 7, 2011, 04:03 PM

Re: How Dangerous is Bird Flu (H5N1) to Global Public Health? Part 2

Nature has made available full free outlooks about influenza and pandemics pareparedness:

This is the summary of the articles (http://www.nature.com/nature/journal...index.html#out )

Influenza by Herb Brody - Nature480, S1 (08 December 2011)
Epidemiology: Racing against the flu by Duncan Graham-Rowe - Nature480, S2?S3 (08 December 2011)
Q&A: The flu catcher by Richard Webby - Nature480, S4?S5 (08 December 2011)
Prevention: Vaccine for all seasons by Jana Schl?tter - Nature480, S6?S8 (08 December 2011)
Drugs: Lines of defence by Roxanne Palmer - Nature480, S9?S10 (08 December 2011)
Public health: Life lessons by Laura Vargas Parada - Nature480, S11?S13 (08 December 2011)
Morbidity: A personal response by Christine Junge - Nature480, S14?S15 (08 December 2011)

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**Laidback Al** · December 16, 2011, 12:33 AM

Re: How Dangerous is Bird Flu (H5N1) to Global Public Health? Part 2

A Family Cluster of H5N1 Cases in Egypt, the Mother Dies and the Child is in Stable Condition

Egypt has just reported a family cluster of H5N1 infections, a mother and child (link). Both individuals became symptomatic on the same day on November 26, 2011. The mother, hospitalized on December 1, 2011 and immediately treated with oseltamivir, died two days later. The child, hospitalized on December 2, seven days after onset, was also treated with oseltamivir. The child is still hospitalized in stable condition and may actually survive.

The fact that this child is still alive is good news for several reasons. First, clinical research has shown that oseltamivir is most effective in saving the lives of H5N1 infected individuals if it is administered within 48 hour of onset. The mother and child both received the antivirals outside this time window, yet the child continues to survive even though the mother did not. Second, this child is still alive and battling an H5N1 infection even though children are more susceptible and get sicker from novel influenza strains because they have not had a long time to build up immunity from exposure to circulating influenza strains. Third, for reasons that are still unclear, numerous children infected with H5N1 in Egypt have survived despite the virulence of the H5N1 virus in human cases in other countries such as Indonesia. Before the media blackouts on disease outbreaks in Egypt, the data on human H5N1 infection in 2009 demonstrated that H5N1 infected children had a high survival rate in Egypt.

The survival of this child will offer a slight glimmer of hope that genetic research on H5N1 infected children in Egypt may lead to some insights in how to protect the world?s populations from an H5N1 pandemic.

**Emily** · December 16, 2011, 04:01 AM

Re: How Dangerous is Bird Flu (H5N1) to Global Public Health? Part 2

This is my limited perspective so it could be totally invalid, but at this point I have the impression that overwork contributed to deaths from the 1918 pandemic and might explain why people in the prime of their working life who were also raising children died from that strain when their children did not. (As opposed to the theory that strong immune systems producing a 'cytokine storm' were the primary drivers of deaths in the 20-40 yr age range.)

I think I posted a newspaper article about the health commissioner of New York during the 1918 pandemic urging people to not go back to work when they first felt recovered. He said that people who did so succumbed to a relapse and urged people to take a few extra days off work to recuperate, (though he admitted it was difficult for some wage earners to do so - caretakers would also be under pressure to get back in action.)

During the Fort Dix outbreak, I think it was a recruit who pushed himself very hard during training that died.

So I agree that the fact that children are surviving H5N1 infections when their caretakers are not is very important. The reason might point to the need for social/material support of wage earners and caretakers for a brief recovery time.

**Giuseppe** · December 16, 2011, 04:55 AM

Re: How Dangerous is Bird Flu (H5N1) to Global Public Health? Part 2

This may be an explaination of some but not all fatal pandemic flu cases in the past.

Children, however, are known to be affected by cykotines 'storms' (ie during respiratory syncytial virus infection), so it is possible that worried parents are much more likely to seek hospital care for their children. At the hospital admission they are early treated with oseltamivir and with other antimicrobial drugs for secondary bacterial co-infection and supportive care, making the prognosis in average more benign than older adults.

Delayed treatment of adult, especially if working-poors, may be one of the reason behind most of the fatal cases of A(H5N1) infection in Egypt and elsewhere.

For the 1918 pandemic, the severity of primary viral pneumonia was not fully explained to date, although social, economical factors could be at least in part responsibile for the poor outcome of youngsters.

Immunological status of population, co-circulation of certain bacterial pathogens - in the pre-antibiotics era - lacking of supportive ventilation support are also part of the clinical pattern, albeit much of the mortality was due to unknown or poor investigated factors.

**Laidback Al** · December 16, 2011, 10:15 AM

Re: How Dangerous is Bird Flu (H5N1) to Global Public Health? Part 2

As an aside to this discussion, the Egyptian mother (referenced in post #10 above) was pregnant when she died. At least five pregnant women have died from H5N1 infection in the last 2-3 years in various countries. Influenza infection is particularly dangerous for pregnant women. For H1N1 and pregnancy see this abstract:

H1N1 2009 influenza virus infection during pregnancy in the USA

**Laidback Al** · December 17, 2011, 12:08 PM

Re: How Dangerous is Bird Flu (H5N1) to Global Public Health? Part 2

Potential for Avian Influenza Reassortment in West Africa?

I believe most discussions and research on reassortant avian influenza viruses have focused on Asia. In a recent article, Circulation of avian influenza viruses in wild birds in Inner Niger Delta, Mali (link, credits tetano), the authors note that year-around circulation of avian influenza viruses in the Inner Niger Delta in Mali in West Africa may indicate that avian influenza reassortment could take place in this area of Africa.

It is worth pointing out that in 2007 there was an H5N1 family cluster of a mother and daughter in Lagos, Nigeria (link). Both died from the infection, although WHO only officially counted the daughter.

Avian influenza surveillance should be increased in the western portion of the African continent.

**Gert van der Hoek** · December 29, 2011, 05:57 AM

Re: How Dangerous is Bird Flu (H5N1) to Global Public Health? Part 2

A characteristic of HP H5N1 is it can infect you via the intestine.

We see reports of cats and dogs with (suspected) H5N1 from time to time. Tigers in a Thai zoo were probably infected after eating infected chickens.
Also sporadic human cases related to food.

This research confirmed this unique feature of H5N1:

Marked endotheliotropism of highly pathogenic avian influenza virus H5N1 following intestinal inoculation in cats

Highly pathogenic avian influenza virus (HPAIV) H5N1 can infect mammals via the intestine

Intestinal inoculation of HPAIV H5N1 resulted in fatal systemic disease.

Announcement

How Dangerous is Bird Flu (H5N1) to Global Public Health? Part 2 (Oct 17, 2011 - Nov 25, 2012)

How Dangerous is Bird Flu (H5N1) to Global Public Health? Part 2 (Oct 17, 2011 - Nov 25, 2012)

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