Wednesday, March 26, 2014

Cambodia’s H5N1 Surge & the `M’ Word

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# 8402

 

This week officials from Vietnam, Cambodia, and the International community are meeting in Phnom Penh, Cambodia to discuss the dramatic increase in H5N1 cases in that country over the past couple of years, along with other avian flu containment and control issues (see VOA report Vietnamese, Cambodian Officials Meet Over Bird Flu Concerns).

 

While H5N1 is the immediate concern, the close proximity and spread of the H7N9 virus in China also looms large for these officials (see Vietnam Girds Against H7N9 As H5N1 Spreads).

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For reasons that are far from clear, the incidence of human infection with the H5N1 virus in Cambodia over the past couple of years far exceeds that seen in neighboring Vietnam, which – in the middle of the last decade – was the world’s hotspot for human cases.

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Mash up of data from WHO & Cambodia’s MOH

 

The reporting of nearly 6 times as many human cases over the past 4 years (46 vs. 8) becomes even more dramatic when you factor in the relative populations of the two countries (Vietnam 89 million, Cambodia 15 million).  Making the rate of human infection roughly 36 times higher in Cambodia since 2011.

 

Overnight the Cambodian Daily carried a report (h/t Crof) intriguingly headlined New Mutation in Bird Flu Virus in Cambodia, which they describe as:

 

The new virus apparently mutated from two existing viruses. It was discovered around the time Cambodia reported its first human infections of 2013.

 

This `mutation’ – more properly a new genotype – isn’t well described in this media report, but appears to be one we’ve discussed previously, which was described last September in Cape Town at the Options VIII Control of Influenza Conference, in an abstract entitled:

 

A new genotype resulting from the reassortment of clade 1.1 and 2.3.2.1 at the origin of the human and animal H5N1 virus cases in Cambodia in 2013


V Duong, S Rith, SV Horm, S Ly, S Sorn, S Chuop, S Buth, R Tsuyuoka, D Laurent, B Richner, H Seng, B Sar, D Holl, P Kitsutani, S Ung, A Tarantola, T Sok , P Buchy

Background: In Cambodia since 2004, A(H5N1) virus has been detected in 39 poultry outbreaks and 32 patients (27 deaths) to May 1, 2013.  Until 2012, all  A(H5N1) strains isolated in Cambodia belonged to clades 1 and 1.1, of which six distinct lineages were identified. Lineage 1 viruses shared the same ancestor with viruses from Thailand, while all the lineages detected since 2005 were closely related to viruses detected in Southern Vietnam.

Materials and Methods: Samples were obtained between January and March 2013. The samples comprised 10 confirmed human cases, 6 poultry outbreak investigations and samples from environmental surveillance of live poultry markets. All samples included in this study tested positive for A(H5N1) virus by real-time RT-PCR. Full genome sequences were generated from 31 strains amplified after inoculation into MDCK cells, embryonated eggs, or directly from the original specimen. Phylogenetic analyses were performed using the maximum likelihood method on all the genes. Antigenic analyses were also performed using reference antisera.

Results: The phylogenetic analysis of 8 genes revealed that the 31 A(H5N1) strains isolated and sequenced in Cambodia in 2013 resulted  from reassortment between clade 1.1 and clade 2.3.2.1 viruses. While the HA and NA genes belong to the clade 1.1, genotype Z, the 6 internal genes are closely related to the viruses of the clade 2.3.2.1 (A/Hubei/1/2011-like). Antigenic analysis demonstrated a significant antigenic drift.

Conclusions: In this study we report the emergence of a new genotype of clade 1.1 A(H5N1) virus in Cambodia associated with a significant antigenic drift. The link between the emergence of this new genotype and the increase in human cases observed in 2013 is yet to be determined. 

 

Last December the  World Health Organization released their monthly Influenza at the human - animal interface report where they discussed this variant and the uptick in human cases.

(excerpts)

This might be due to improvements in surveillance and physician awareness or to a potential increased circulation of the virus in poultry. The case fatality rate among reported cases, however, has decreased (54% in 2013 compared with 90% over all previous years).

Before 2013, H5N1 viruses from clade 1.1 predominated in Cambodia. Analysis of isolates from human cases and birds from the beginning of 2013 revealed the emergence of a new H5N1 genotype resulting from the reassortment of clade 1.1 and clade 2.3.2.1 viruses.

The link between the emergence of this reassortant virus and the increase in human cases observed in 2013 is yet to be determined.

 

While the media loves to use the `M’ word (mutation), the reality is influenza viruses are constantly evolving, perpetually producing new genotypes and variants. A few thrive and spread, but most are evolutionary failures, unable to compete against more biologically `fit’ variants.

 

More than 20 clades and subclades of  the H5N1 virus have been identified since 1996, and more are to be expected. This constant evolution is something we’ve looked at often, including Moving Viral Targets & EID Journal: The Expanding Variants Of H5N1.

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Evolution of H5N1  -  NOTE: Not all of these clades continue to circulate.

 

 

Although this new genotype may be behind the uptick in Cambodian H5N1 cases, there are other possibilities as well, some of which are explored in the following Radio Australia Interview  (h/t Carol@SC on the Flu Wiki).

(Transcript & MP3 Audio at the link below)

 

Rising number of bird flu cases in Cambodia under scrutiny

Updated 26 March 2014, 13:34 AEST

Cambodia reported 14 deaths last year from the bird flu strain H5N1.

(Credit: ABC)

It was the highest number of human cases in the world and more than the total that Cambodia had recorded, since H5N1 was first detected there a decade ago.

So far this year, another four Cambodians have died from avian influenza.

This week, officials from Cambodia, Vietnam and international agencies have been meeting in Phnom Penh to try to work out why the numbers are higher and what to do about it.

Reporter: Robert Carmichael

Speakers: Dr Dennis Carroll, USAID; Lotfi Allal, FAO; market vendor Ly Mey


While scattered H5N1 outbreaks continue to plague Vietnam, and the recent introduction of clade 2.3.2.1C has created a snag in their vaccination program (see Vietnam Reporting H5N1 Poultry Vaccine `Failures’), eight years ago - through a combination of massive educational and regulatory efforts - they went from being the worst afflicted country in the world to being viewed as the `poster child’ for successful bird flu containment.

 

Hopefully some of the lessons learned from that experience can be used to do the same for Cambodia.