Seroprevalence Study: Avian Flu In Chinese Pigs

 

Since pigs can be infected by more than one flu virus at the same time, the potential exists for two viruses to swap genetic material (reassort), resulting in a new hybrid strain.

 

# 6796

 

Although we tend to think of H5N1 whenever someone mentions `avian flu’, in truth there are many different avian influenza viruses.  If you go back far enough, all influenza A strains – even those thought of today as primarily adapted to humans, equines, or swine – appear to have an avian origin.

 

Influenza A viruses have 8 gene segments (PB2, PB1, PA, HA, NP, NA, M1, M2, NS1, NS2) and are broadly categorized by their HA (hemagglutinin) and NA (neuraminidase) genes.

 

With the recent discovery of H17N10 (see A New Flu Comes Up To Bat), scientists have now identified 17 different serotypes of Hemagglutinin (HA) and 10 serotypes of Neuraminidase (NA), which make many different combinations of HA and NA proteins possible.

Thus far, only about 100 of these combinations have been isolated in nature.

 

But the flu universe is far more diverse than that might lead to you believe, as influenza’s 8 gene segments are largely interchangeable parts. If you were to take two different influenza A viruses (say H3N2 and H5N1) and reshuffle them using reverse genetics, you can come up with 254 possible reassortments.

 

And within each of these HA/NA combinations you can have multiple clades (genetically distinct families), and within each clade, many minor variants – all of which makes for tremendous variety in these viruses.

 

Many of the the H1, H2, and H3 viruses have adapted to human physiology, but we occasionally see infection by other `novel’ strains. Most worrisome, due to its high fatality rate, is H5N1.  But we occasionally see (usually mild) infections by other avian strains.

 

MMWR: Mild H7N3 Infections In Two Poultry Workers - Jalisco, Mexico)

EID Journal: Human Infection With H10N7 Avian Influenza

PLoS One: Seroprevalence Of H9N2 In Poultry Workers – Pune, India

 

Last year scores of dead seals were discovered along the shoreline of New England, predominantly from the North Shore of Massachusetts to the southern coast of Maine.  Investigations showed (see mBio: A Mammalian Adapted H3N8 In Seals) their deaths to be due to a variant of the H3N8 avian flu strain, versions of which are known to also infect horses and dogs.

 

With the propensity of these avian strains to evolve and adapt, scientists are understandably very interested in any avian flu virus that appears to be moving towards `humanization’.

 

While it is possible for a flu virus to jump directly from birds to humans, often it requires an intermediate host to aid in its development. The graphic below illustrates that swine – which are generally susceptible to human and avian flu viruses - are considered excellent mixing vessels’ for influenza viruses.

 

 

The H1N1 `swine flu’ virus of 2009 kicked around in pigs for up to a decade before it adapted well enough to human physiology to spark a human pandemic. Over the past few years we’ve watched attempts by three other swine `variant’ viruses (H1N1v, H1N2v, H3N2v) to jump to mankind. 

 

Which makes the active surveillance of swine a potentially important tool for the early detection of emerging influenza viruses.

 

Unfortunately, while there are some surveillance systems in place, only a tiny fraction of the world’s swine population is actively monitored  (see Helen Branswell’s SciAm Article from late 2010 called Flu Factories).

 

All of which serves as prelude to a new study, recently published in the Journal of Clinical Microbiology, that found low levels of H3, H4, and H6 subtypes of avian influenza in Chinese pigs. Somewhat reassuringly, evidence of infection with the H5N1 virus was not found.

 

These H3, H4, and H6 avian viruses were not seen in a similar study done in 2001, suggesting their arrival into the swine population may be a recent development.

 

 

Seroepidemiological Evidence of Avian Influenza A Virus Transmission to Pigs in Southern China

Shuo Su, Wenbao Qi, Jidang Chen, Wanjun Zhu, Zhen Huang, Jiexiong Xie, and Guihong Zhang

J. Clin. Microbiol. published ahead of print 21 November 2012 doi:10.1128/JCM.02625-12

ABSTRACT

Recently, three novel avian-origin swine influenza viruses (SIVs) were first isolated from pigs in Guangdong Province, southern China, yet little is known about the seroprevalence of avian influenza among pigs in southern China. Here, we report for the first time the seroprevalence of avian H3, H4, and H6 influenza viruses in swine populations and the lack of seroepidemiological evidence of avian H5 influenza transmission to pigs in China.

 

A copy of the study can be downloaded here.

 

The American Society for Microbiology has published a press release with more information, excerpts of which you’ll find below:

 

 

 

Pigs in southern China infected with avian flu

WASHINGTON, DC – December 19, 2012 -- Researchers report for the first time the seroprevalence of three strains of avian influenza viruses in pigs in southern China, but not the H5N1 avian influenza virus.  Their research, published online ahead of print in the Journal of Clinical Microbiology, has implications for efforts to protect the public health from pandemics.

 

Influenza A virus is responsible both for pandemics that have killed millions worldwide, and for the much less severe annual outbreaks of influenza. Because pigs can be infected with both human and avian influenza viruses, they are thought to serve as “mixing vessels” for genetic reassortment that could lead to pandemics, and pigs have been infected experimentally by all avian H1-H13 subtypes. But natural transmission of avian influenza to pigs has been documented only rarely.

 

In the study, from 2010-2012, Guihong Zhang and colleagues of the College of Veterinary Medicine, South China Agricultural University, Guangzhou, People’s Republic of China, tested 1080 21-25 week old pigs for H3, H4, H5, and H6 subtypes of avian influenza virus, and H1 and H3 subtypes of swine influenza virus. Thirty-five percent of the serum samples were positive for H1N1, and 19.7 percent were positive for H3N2 swine flu virus, and 0.93 percent, 1.6 percent, and 1.8 percent were positive, respectively, for the H3, H4, and H6 subtypes of avian influenza A virus. However, no serum samples collected in 2001 were positive for any of these viruses, indicating that transmission into swine was recent.

 

Given the recent transmission of avian influenzas into swine, “We recommend strongly that the pork industry worldwide should monitor the prevalence of influenza in pigs, considering their important role in transmitting this virus to humans,” says Zhang.

 

Previously, novel reassortant H2N3 influenza viruses were isolated from US pigs, which “were infectious and highly transmissible in swine and ferrets without prior adaptation,” according to a 2009 paper in the Journal of Molecular and Genetic Medicine by Wenjun Ma et al. Those viruses resembled, but were not identical to the H2N2 human pandemic virus of 1957.

 

 

The ability of influenza viruses to evolve, mutate, or reassort in swine hosts has been a frequent topic of discussion in this blog.  For more on this, you may wish to revisit:

 

H3N2v: When Pigs Flu

You Say You Want An Evolution?

The (Swine) Influenza Reassortment Puzzle

»» Read More

CIDRAP: Children & Middle-Aged Most Susceptible To H3N2v

Credit Wikipedia

 

# 6489

 

Robert Roos of CIDRAP has an excellent report on a study – published on Aug 7th in The Journal of Infectious Diseases – that looks at pre-existing, and vaccine-induced immunity to the emerging H3N2v swine flu virus by age cohorts.

 

This serological study, conducted in Canada, is called :

 

Cross-reactive and vaccine-induced antibody to emerging swine influenza A(H3N2)v

Danuta M. Skowronski, Naveed Z. Janjua, Gaston De Serres3, Dale Purych, Vladimir Gilca, David W. Scheifele, Marc Dionne, Suzana Sabaiduc, Jennifer L. Gardy, Guiyun Li, Nathalie Bastien, Martin Petric, Guy Boivin and Yan Li

 

 

Below is Robert’s report on these findings, and as I’m hardly likely to improve upon his work, I’ll simply invite you to follow the link below and read:

 

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

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.

(Continue . . .)

 

Robert’s story mentioned earlier studies with similar findings, and you can find details on them in these earlier blogs:

 

Last April in MMWR: Antibodies Cross-Reactive to Influenza A (H3N2) Variant Virus, we saw a study that found that children under the age of ten were practically devoid of antibodies to this virus, and were likely the most susceptible to infection.

 

A few months before, in Eurosurveillance: Older People May Be Susceptible To The H3N2v Virus), we saw evidence that the moderate levels of immunity detected in adolescent and young adult populations declined with age.

 

In other H3N2v news, Lisa Schnirring of CIDRAP has a excellent roundup, including the release of new interim clinician guidelines, the poor reliability of RIDTs (Rapid Influenza Detection Tests) with this virus, and an age breakdown of confirmed cases that now includes 10 adults.

 

CDC updates novel H3N2 info for clinicians

Lisa Schnirring Staff Writer

Aug 10, 2012 (CIDRAP News) – The US Centers for Disease Control and Prevention (CDC) today reported that it has received 153 reports of novel H3N2 infections (H3N2v) since illnesses started surfacing in the middle of July, nearly all of them in people who had contact with pigs or were around pigs at fairs.

 

In another development, the CDC issued new information on H3N2v for clinicians, including an evaluation of rapid influenza tests that found their sensitivity varies greatly, and the agency urged clinicians not to use negative results as the basis for treatment.

(Continue . . . )

 

 

A blogger’s Note:

 

The slow emergence of this swine H3N2v virus into the human population is a fascinating story, and one that certainly deserves ongoing coverage.  But at the same time, the last thing this story needs is unwarranted hype.

 

According to the CDC, this virus has not adapted well enough to human physiology to spark a pandemic.  Nearly all confirmed cases appear to be the result of direct contact with an infected pig.

 

Sustained and efficient Human-to-Human transmission does not appear to be occurring at this time.

 

The caveat being, that over time, that could change.

 

For now, this virus is less a public health threat story and more an opportunity for us to learn how these types of viruses evolve in swine and (on rare occasion) seep into the human population.

 

A cautionary tale, if you will, on how nature’s laboratory is open 24/7 - constantly trying out new viral combinations - looking for an evolutionary advantage.

 

The dilemma, from my standpoint, is how to cover this story responsibly. 

 

Rather than rush to post a blog every time we get an updated case count, for my own sanity, I’ve decided only to blog on the H3N2v virus when there is something more substantial to report.

 

This weekend I’ll explore the possibility of keeping a daily update `State Confirmed H3N2v Cases’ in my sidebar, at least until that becomes too unwieldy.

 

Even so, I’m sure H3N2v will get ample attention in these pages.

 

As we wait to see what this H3N2v virus ends up doing - between seasonal flu, bird flu, swine flu, seal flu, and bat flu, plus non-flu related stories - I’m confident there will be no shortage of topics to blog about.

»» Read More

PLoS One: Seroprevalence Of H9N2 In Poultry Workers – Pune, India

 

 

# 6337

 

While H5N1 gets the lion’s share of the media’s attention, there are other influenza viruses in the wild believed capable of sparking the next flu pandemic.  Over the past dozen years we’ve seen a number of avian flu strains that have made limited jumps to human hosts.

 

• In 2003, an outbreak of H7N7 at a poultry farm in the Netherlands went on to infect at least 89 people (mostly mildly, but 1 death), and many more may have been infected subclinically.
• In Egypt - in 2004 -  2 infants were shown to be infected by the H10N7 avian flu virus.
• In 2006 1 person in the UK was confirmed to have contracted H7N3, and the following year, 4 people tested positive for H7N2 – both following local outbreaks in poultry.

 

But in terms of greatest concern, the closest runner up to H5N1 is probably H9N2 – which is known to have infected a handful of humans, mostly in Asia.

 

To date, most of these cases have produced relatively mild illness.  

 

Nevertheless, the World Health Organization  has announced that work has begun on the creation of an H9N2 candidate vaccine (see WHO Report : Antigenic & Genetic Characteristics of H5N1 & H9N2 Viruses).

 

Last year, in PNAS: Reassortment Potential Of Avian H9N2 , researchers looked at the reassortment potential of the avian H9N2 virus and H1N1, generating four reassortant viruses, three of which showed efficient respiratory droplet transmission in the ferret model.

 

These authors had previously successfully created laboratory reassortments between seasonal H3N2 and H9N2. 

 

Experiments that are, in many ways, similar to the H5N1 experiments of Fouchier and Kawaoka that have caused such a stir these past few months, albeit on a (thus far) much-less-pathogenic flu virus.

 

These successes (and others, see PNAS: Reassortment Of H1N1 And H9N2 Avian viruses), along with the wide geographic distribution of the H9 avian virus in poultry across Asia and the Middle East, have led many researchers to call for better research and surveillance on this avian strain.

 

Which brings us to a new study, published late last week in the journal Plos One, that looks at the prevalence of antibodies to the H9N2 strain among poultry workers – and the general population – in Pune, India.

 

Avian Influenza H9N2 Seroprevalence among Poultry Workers in Pune, India, 2010

Shailesh D. Pawar, Babasaheb V. Tandale, Chandrashekhar G. Raut, Saurabh S. Parkhi, Tanaji D. Barde, Yogesh K. Gurav, Sadhana S. Kode, Akhilesh C. Mishra

PLoS ONE 7(5): e36374. doi:10.1371/journal.pone.0036374

Abstract

Avian influenza (AI) H9N2 has been reported from poultry in India. A seroepidemiological study was undertaken among poultry workers to understand the prevalence of antibodies against AI H9N2 in Pune, Maharashtra, India.

 

A total of 338 poultry workers were sampled. Serum samples were tested for presence of antibodies against AI H9N2 virus by hemagglutination inhibition (HI) and microneutralization (MN) assays.

 

A total of 249 baseline sera from general population from Pune were tested for antibodies against AI H9N2 and were negative by HI assay using ≥40 cut-off antibody titre.

 

Overall 21 subjects (21/338 = 6.2%) were positive for antibodies against AI H9N2 by either HI or MN assays using ≥40 cut-off antibody titre. A total of 4.7% and 3.8% poultry workers were positive for antibodies against AI H9N2 by HI and MN assay respectively using 40 as cut-off antibody titre.

 

This is the first report of seroprevalence of antibodies against AI H9N2 among poultry workers in India.

 

 

Although a bit of a gray area, an antibody titer level of ≥40 is generally assumed to be suggestive of a previous (possibly sub-clinical) infection by a specific virus.

 

Interestingly, none of the 249 sera samples from the general population showed elevated antibody titers to the H9N2 virus (using the ≥40 cut-off standard), but among poultry workers, 21 of the 338 sera samples (6.2%) tested positive for H9N2 antibodies.

A fairly low number given the amount of exposure,  but indicative that some transmission of the virus to humans appears to be taking place.

The authors warn that:

 

The evidence of AI (H9N2) in poultry market may provide the opportunity for human infections and the possibility of reassortment with the existing poultry AI viruses including HPAI H5N1 virus.

 

Warnings over the pandemic potential of the H9N2 virus are not new. A few notable stories from the past include:

 

• In December 2008 I ran a blog featuring an interview in which world famous Hong Kong virologist Malik Peiris cautioned that the H9N2 virus may be circulating far more commonly than we believe. Revisiting A Malik Peiris Interview On H9N2.

• In January of 2010, in H9N2: The Other Bird Flu Threat, I wrote about the World Health Organization  recommending the creation of a candidate vaccine virus for H9N2.

• And in November 2010, in Study: The Continuing Evolution Of Avian H9N2, we looked at computer modeling that suggested that the H9N2 virus moving towards becoming more `human-adapted’.

 

 

Unlike the H7 and H5 avian flu strains, poultry (and swine) infections by the H9N2 virus are not required to be reported to the OIE.  

 

Admittedly, the next influenza virus to successfully jump species could come out of left field, as we saw in 2009 with the H1N1 swine flu.

 

 

Which is why the global monitoring of influenza viruses - in humans, on the farm, and in the wild - remains crucial if we hope to detect, and prepare for, the next pandemic at the earliest possible moment.

»» Read More

Eurosurveillance: Cross Reactive Antibodies to H3N2v In Norway

 

# 6321

 

 

A newly published seroprevalence study out of Norway that looks for cross reactive antibodies (suggestive of potential immunity) against the H3N2v swine flu strain has produced some surprising results.

 

The H3N2v (variant) strain began showing up in the United States in the middle of 2011, and since that time has been isolated in 13 people across 5 states.

 

Some, but not all, of the victims had exposure to swine, leading investigators to suspect limited person-to-person transmission might be occurring.

 

It is too soon to know if this strain has `legs’, and will continue to circulate in humans and perhaps eventually pose a more serious public health threat.

 

For more background on this emergent flu strain you may wish to revisit (H3N2v: Three’s A Crowd).

 

 

Given the possibility that this new strain could gain a foothold in the human population, the CDC has been working on a seed vaccine strain, and investigators around the world have been testing to see what age groups might be most susceptible to this virus.

 

Early indications have been that those under the age of 12 are at greatest risk, as 12 of the 13 known cases have involved young children.

 

Antigenically similar H3 viruses circulated through the mid 1990s, which might have left behind some degree of immunity to those exposed. Those born after 1999 would not be expected to carry those antibodies.

 

In April of 2012 we saw a study (see MMWR: Antibodies Cross-Reactive to Influenza A (H3N2) Variant Virus) that found that children under the age of 10 had few or no cross-reactive antibodies to the H3N2v strain, suggesting they would be the most vulnerable age group to the virus.

 

Based on the small sampling of tests conducted, approximately 1/3rd of those aged 10–49 years displayed cross-reactive antibodies that might provide some protection against infection from the H3N2v virus.

 

Seroprevalence testing on those aged 50 to 65 was not included in this particular study. Another study, published in January, found a similar lack of cross-reactive antibodies among children.

 

All of which serves as prelude to today’s study that appears in this week’s Eurosurveillance Journal.

 

Eurosurveillance, Volume 17, Issue 19, 10 May 2012

Rapid communications

Age-dependent prevalence of antibodies cross-reactive to the influenza A(H3N2) variant virus in sera collected in Norway in 2011

K Waalen , A Kilander, S G Dudman, R Ramos-Ocao, O Hungnes

---

Antibody cross-reactivity to the influenza A(H3N2) variant virus recently reported in the United States, was investigated in Norwegian sera. Seroprevalence was 40% overall, and 71% in people born between 1977 and 1993.

 

The most susceptible age groups were children and people aged around 50 years. The high immunity in young adults is likely to be due to strong priming infection with similar viruses in the 1990s. More research is needed to explain the poor immunity in 45–54 year-olds.

 

While their data is in pretty good agreement with the two other studies mentioned above, quite unexpectedly they found that levels of seroprotective antibodies to the H3N2v virus were substantially lower among those aged 45 to 54 years than in other adult age brackets. 

 

The authors have no straightforward explanation for this `gap’ in immunity among those born between the late 1950s and early 1960s, and call for more research into this surprising finding.

 

As for the pandemic potential of this virus, they offer this hopeful assessment in their conclusion:

 

The considerable prevalence of cross-reactive antibodies suggests that there may be a limit to the epidemic potential of these viruses in their current form.

 

Of course, the standard caveats apply.

Cross reactive antibodies are suggestive of possible immunity, but don’t always correlate to actual protection against infection or illness.  And the H3N2v virus – like all flu viruses – is constantly changing and evolving.

 

For more background on variant flu viruses, you may wish to visit the following CDC webpage:

 

Key Facts about Human Infections with Variant Viruses (Swine Origin Influenza Viruses in Humans)

Questions & Answers

On this Page

• What is swine influenza?
• What is a variant influenza virus?
• Can humans be infected with swine influenza viruses?
• How common is it for humans to be infected with influenza viruses that normally spread in swine?
• Why are human infections with variant viruses of concern?
• What symptoms do people have when they are infected with variant viruses?

• Can people catch swine flu/variant flu from eating pork?
• How are variant influenza viruses spread?
• How can human infections with variant influenza viruses be diagnosed?
• What medications are available to treat variant flu infections in humans?
• What other examples of outbreaks with influenza viruses that normally circulate in swine are there?
• Was the “2009 H1N1” pandemic virus the same as previously circulating human H1N1 viruses?

»» Read More

Taiwan: Three Poultry Workers Show H5N2 Antibodies

 

Photo Credit – FAO

# 6297

 

 

There are several variations of this news report floating across the wires this morning, but in the end, it may turn out that there is less to this story than at first appears.

 

The gist of the story is that three poultry workers and/or animal quarantine officers who worked at a farm where the H5N2 virus was recently discovered have tested positive for antibodies to the H5N2 virus.

 

H5N2, while an avian influenza virus, is currently considered a far less dangerous pathogen than its infamous cousin, H5N1.

 

But all H5 viruses (along with H7s) are reportable to the OIE because of their potential to evolve into more dangerous viruses, particularly when they are allowed to proliferate in large flocks of poultry.

 

First a link to the Taiwan story, then I’ll return with more:

 

3 poultry workers, quarantine officers show antibodies for H5N2

2012/04/22 21:05:42

Taipei, April 22 (CNA) The Centers for Disease Control (CDC) confirmed Sunday that three poultry workers and officials working in animal quarantine have tested positive for antibodies for the H5N2 strain of avian influenza.

However, all three people are healthy and none have developed any flu symptoms, CDC Deputy Director-General Chou Jih-haw said, adding that there is no public health risk of human-to-human transmission.

(Continue . . .)

 

While antibodies to the H5N2 virus have been detected a few times in humans in the past, the virus has never been shown to cause illness in human hosts. 

 

A couple of studies in the past include:

 

J Epidemiol. 2008;18(4):160-6. Epub 2008 Jul 7.

Human H5N2 avian influenza infection in Japan and the factors associated with high H5N2-neutralizing antibody titer.

Ogata T, Yamazaki Y, Okabe N, Nakamura Y, Tashiro M, Nagata N, Itamura S, Yasui Y, Nakashima K, Doi M, Izumi Y, Fujieda T, Yamato S, Kawada Y.

Arch Virol. 2009;154(3):421-7. Epub 2009 Feb 3.

 

Serological survey of avian H5N2-subtype influenza virus infections in human populations.

Yamazaki Y, Doy M, Okabe N, Yasui Y, Nakashima K, Fujieda T, Yamato S, Kawata Y, Ogata T.

 

 

While suggestive of prior H5N2 infection, there is precious little evidence to link any significant or serious human illness to the H5N2 virus.

 

Complicating the story out of Taiwan is the fact that, starting in 2010, Taiwan began offering soon-to-expire H5N1 vaccine to high risk members of their population, including poultry workers and animal quarantine officers. 

 

See Focus Taiwan article from Sept 1st, 2010 titled CDC begins national bird flu vaccination program for details.

 

 

So while it is possible that these three workers acquired H5N2 antibodies from direct exposure to infected poultry, it may simply be that their tests are showing cross-reactivity to H5N1 antibodies created by the bird flu vaccine they received.

 

It has also been suggested that a history of seasonal influenza vaccinations could produce H5N2-neutralizing antibody positivity as well.

 

Which leaves us with an intriguing story, but one with a lot of possible holes in it.

 

For more on the H5N2 virus in Taiwan, you may wish to revisit:

 

WHO: Human Risk From H5N2 Is Low

Taiwan: H5N2 At Poultry Farm

»» Read More

H5N1 Seroprevalence Among Jiangsu Province Poultry Workers

 

Study location Jiangsu Province – Credit Wikipedia

 

# 6291

 

 

We’ve a new study that adds incrementally to our knowledge base on human infection by the H5N1 bird flu virus that appeared in BMC Infectious Diseases yesterday. The results of which, I suspect, will end up being used by both sides of the The Great CFR Divide.

 

 

Researchers interviewed and took blood samples from 306 poultry workers from three counties in Jiangsu Province, China between July 1st and August 15th, 2010. None of the workers reported serious respiratory illness in the past, and all dealt with un-vaccinated poultry on routine basis.

 

The open access study may be viewed at:

 

Seroprevalence of avian influenza A (H5N1) virus among poultry workers in Jiangsu Province, China: an observational study

Xiang Huo, Rongqiang Zu, Xian Qi, Yuanfang Qin, Liang Li, Fenyang Tang, Zhibin Hu and Fengcai Zhu

BMC Infectious Diseases 2012, 12:93 doi:10.1186/1471-2334-12-93

Published: 18 April 2012

Abstract (provisional)

Background

Since 2003 to 06 Jan 2012, the number of laboratory confirmed human cases of infection with avian influenza in China was 41 and 27 were fatal. However, the official estimate of the H5N1 case-fatality rate has been described by some as an over estimation since there may be numerous undetected asymptomatic/mild cases of H5N1 infection. This study was conducted to better understand the real infection rate and evaluate the potential risk factors for the zoonotic spread of H5N1 viruses to humans.

Methods

A seroepidemiological survey was conducted in poultry workers, a group expected to have the highest level of exposure to H5N1-infected birds, from 3 counties with habitat lakes of wildfowl in Jiangsu province, China. Serum specimens were collected from 306 participants for H5N1 serological test. All participants were interviewed to collect information about poultry exposures.

Results

The overall seropositive rate was 2.61% for H5N1 antibodies. The poultry number was found associated with a 2.39-fold significantly increased subclinical infection risk after adjusted with age and gender.

Conclusions

Avian-to -human transmission of avian H5N1 virus remained low. Workers associated with raising larger poultry flocks have a higher risk on seroconversion.

 

 

 

The researchers used two different H5N1 reference antigen strains for the seroprevalence analysis; one from 2010 A/Hubei/1/10 (clade 2.3.2)  and an older one from 2005 A/Anhui/1/05 (clade 2.3.4).

 

While the total seropositive rate was 2.61% (95%CI, 1.14%–5.09%), it turned out that none of the blood samples tested positive for the newer (A/Hubei/1/10) strain.

 

Only antibodies to the older A/Anhui/1/05 strain were detected.

 

And of the three locations tested (Gaochun, Jianhu and Gaoyou counties) the percentage of workers testing positive ranged from zero (Gaochun) to 5.38% (95%CI, 2.19%–10.78%) in Gaoyou.

 

In their discussion, the authors state:

 

Several serological studies have been conducted to assess the transmission of H5N1 virus in poultry workers. The reported seropositive rates vary from 0 to 10% [9-11]. In the present study, the overall positive rate we found was 2.61% and in different sampling districts the rates varied from 0 to 5.38%.

 

Many factors could be responsible for the variability, such as the H5N1 infection rate and vaccination rate of the poultry, the precautions and job duties of the workers. In our study, poultry number was identified as a novel risk factor associated with human infection with avian H5N1 virus, which could be accounted for the distinction of seropositive rate among districts and studies.

<SNIP>

Conclusions

Avian-to –human transmission of avian H5N1 virus remained low. Workers associated with raising larger poultry flocks have a higher risk of seropositivity.

 

 

This is a small sampling - a little over three hundred blood tests conducted across three counties in Northern China – so one must be careful in extrapolating these numbers across a wider population.

 

But the lack of seropositivity among poultry workers in Gaochun county suggests a good deal of variability, even among high risk populations.

 

Which means you can’t simply multiply the population of endemic regions by 2.61% in order to come up with a reasonable estimate of the number infected.

 

And there’s a lot we don’t know about the road to achieving seropositivity, including viral load required, mode of infection (or exposure), and differences in the pathogenicity and transmissibility of various clades of the virus.

 

Earlier this week in Differences In Virulence Between Closely Related H5N1 Strains, we looked at two closely related H5N1 strains which produced decidedly different pathogenesis in mice and ducks.

 

With at least 20 clades of the virus identified, and a good deal of genetic variation within each clade, it makes it very difficult to make any general statement about the virulence or transmissibility of the H5N1 virus.

 

Today’s study shows that low levels of H5N1 seropositivity among some poultry workers in China exists.

 

But it is neither uniform nor is it universal. 

 

It’s another data set to consider, along with the handful of other studies we’ve seen. But does not provide a definitive answer, one way or the other, on the transmissibility of the H5N1 virus.

 

For more on H5N1 seroprevalence studies, and the controversy over the Case Fatality Rate of the H5N1 virus, you may wish to revisit:

 

mBio: Mammalian-Transmissible H5N1 Influenza: Facts and Perspective

Science: Peter Palese On The CFR of H5N1

Study: Subclinical H5 & H9 Infections In Humans

The Thailand Serological Study

»» Read More

ICEID: Another H5N1 Seroprevalence Study To Ponder

 

 

# 6218

This week I hope to highlight some of the ICEID 2012 abstracts (see ICEID 2012: Abstracts & Program) of particular interest to Flublogians.

 

With the recent controversy over the seroprevalence of H5N1 virus (see Science: Peter Palese On The CFR of H5N1 & mBio: Mammalian-Transmissible H5N1 Influenza: Facts and Perspective) we’ve seen estimates ranging from there being relatively few undetected human cases of H5N1 infection to `millions’.

 

If there are mild or subclinical infections with the virus going undetected, the best way to find them is to look for antibodies in the blood of those who have had substantial exposure to poultry.

 

Which is precisely what researchers at International Centre for Diarrhoeal Disease Research Bangladesh (ICDDR,B), Bangladesh’s Institute of Epidemiology, Disease Control and Research (IEDCR), and the CDC did.

 

They performed microneutralization assays on workers from 89 poultry farms with confirmed H5N1 outbreaks and 3 live bird markets reporting high poultry mortality to detect neutralizing antibodies in sera using A/Bangladesh/207095/2008 (H5N1).

 

The following abstract can be found on page 116 of the 2012 ICEID Abstract, I’ve just excerpted the conclusion.

 

Board 183. Sero-prevalence of H5N1 Antibodies among Poultry Workers in Bangladesh, 2008–2009

S. Nasreen, S.U. Khan, E. Azziz-Baumgartner, K. Hancock, J.M. Katz, V Veguilla, D. Wang , M. Rahman, A. Alamgir, E.S. Gurley, K. Sturm-Ramirez T.M. Uyeki , S.P. Luby

Conclusions: Despite extensive poultry
exposures, no serological evidence of H5N1 virus infection was found among farm or market poultry workers during 2008-09.

However, the recent cases of human H5N1 infection detected in Bangladesh and the continued circulation of H5N1 among poultry warrants continued surveillance among a larger cohort of poultry workers to monitor the risk of avian-to-human H5N1 virus transmission.

 

 

It should be noted that since the beginning of the year, Bangladesh has detected 3 H5N1 infections among live poultry market workers through routine surveillance (see IEDCR On The Bangladesh H5N1 Cases).

 

All appear to have had mild to moderate illness, and have recovered.

 

With multiple clades of the H5N1 virus in circulation around the world - and constantly mutating - what may have been true in 2009 may not hold true today. 

So ongoing seroprevalence studies in Bangladesh, and other regions where the virus is endemic, are sorely needed.

»» Read More

Route Of Shenzhen Bird Flu Infection Unclear

 

    # 6046

 

 

 

The means by which a 39-year-old bus driver from the city of Shenzhen in Guangdong Province, China came to contract a fatal H5N1 infection remain unclear according to a report in today’s China Daily.

 

The victim, named Chen, was reported yesterday to have died after spending nearly a week in a coma at a local hospital (see Shenzhen Bird Flu Suspect Dies).

 

Early reports indicate he neither had contact with poultry, or had traveled outside of the city, in the past 30 days. First an excerpt from the Xinhua news report, then I’ll return with more.

 

Cause of bird flu death in S China still unclear

Updated: 2012-01-01 21:06

(Xinhua)

GUANGZHOU - Health authorities in south Guangdong province have yet to find the cause of the highly pathogenic H5N1 virus, commonly known as bird flu, that led to the death of a bus driver, a local disease control official said Sunday.

 

The 39-year-old man surnamed Chen in Bao'an district of Shenzhen was hospitalized for fever on December 21 and tested positive for the H5N1 avian influenza virus. He died of multiple organ failure Saturday afternoon, the Guangdong Health Department said in a statement.

 

The department also said that during the previous month prior to his fever, he had no direct contact with poultry and hadn't traveled out of the city.

 

Chen's wife said he had a habit of doing morning exercises every day near a wetland park and an artificial lake not far from his home, but "no proof has been found that his infection is connected with the migratory birds there," He Jianfeng, director of the Epidemics Studies Institute of the Guangdong Disease Control Center, said Sunday.

 

"We also don't know whether he had eaten poultry before he fell ill," He said.

(Continue . . .)

 

 

Determining the likely route of infection in a specific bird flu patient has always been tricky, and often the `official’ determination is based on circumstantial evidence.  

 

Direct contact with sick or dead birds has been the most common mode cited over the years, even in some cases where the aforementioned birds were not identified or confirmed to be infected with the virus.

 

And often, that was probably a reasonable enough assumption.  Occam's razor being – the simplest explanation is most likely the correct one.

 

Without specific regard to today’s case, it is worth noting that we’ve also seen serological evidence of subclinical, or asymptomatic infection with the H5N1 virus in China and in Thailand, and even among some people who were unlikely to have acquired it directly from poultry.

 

Last December, in Study: Subclinical H5 & H9 Infections In Humans, we saw a report out of China on the detection of antibodies to both H9 and H5 avian influenza viruses among a small number of villagers in and around Beijing, China.

 

The study was titled:

 

Infection With Multiple Avian Influenza Viruses in a Man Without Poultry-Handling Practices Suggesting an Increased Probability of Emergent Pandemic Influenza Virus in General Population

Peng Yang, Weixian Shi, Shujuan Cui, Yi Zhang, Xiujun Liu, and Quanyi Wang

 

 

In September of last year we saw a study that reported the results of this kind of serological testing conducted in a rural village in Thailand in 2008 (see Bangladesh To Share H9N2 Bird Flu Virus). 

 

Out of 800 villagers tested, the authors found 4.7% were seropositive for the Hong Kong H9N2 avian strain, 5.6% had antibodies to A/Thailand/676/2005 H5N1 bird flu, and 3.5% were shown to be seropositive to A/Thailand/384/2006 H5N1.

 

The implications of these studies are that human infection with these avian viruses – while still rare – is probably more common that current surveillance and reporting suggests.

 

And that opens the possibility, at least, that asymptomatic H5N1 infections could (in rare cases) provide a silent route of transmission of the virus.

 

Again, the evidence here is both scant, and primarily circumstantial. And there is no evidence to suggest sustained or efficient transmission.

 

For now, the H5N1 virus appears poorly adapted to human physiology. And while the concern is that, over time, that could change, it is also possible that this virus will never adapt fully to humans.

 

But with the recent laboratory successes in turning the H5N1 virus into a more easily transmissible pathogen (see The H5N1 Research Debate Goes On), there are renewed concerns in the scientific community that this avian virus may one day evolve enough to pose a serious pandemic threat to mankind.

»» Read More

Study: Subclinical H5 & H9 Infections In Humans

 

 

 

# 5994

 

 

As of November 29th, 2011 the World Health Organization has logged 571 confirmed human infections with the H5N1 virus, with 335 deaths. The case fatality rate (CFR) – based on the numbers we know – is a staggeringly high 58.6%.

 

Mash up of WHO data

 

But most observers will grant that these totals are not likely to represent the entire burden of the H5N1 virus in humans around the world. As with any other illness or disease, surveillance is imperfect, and not every case is counted.

 

Surveillance across much of Asia and the Middle East - where the virus is known to be endemic - is spotty at best, and many countries do not have the laboratory facilities, budget, or political will to adequately screen for the virus.

 

It has been suggested that the reason the CFR of this virus is perceived to be so high is because milder cases are more likely to go unrecognized or unreported.

 

 

And while that sounds reasonable, without evidence of a substantial number subclinical or mild infections, you can’t just leap to that conclusion.

 

Finding that evidence would be a good news-bad news proposition.  

 

The good news is that it would reduce the CFR of the virus, albeit perhaps not by a lot.

 

The bad news is that it could indicate the virus is slightly better adapted to human physiology than we currently believe, and that it might even be transmitting at low levels.

 

Last night CIDRAP News carried a small summary of a letter that appears in the Dec. 5th Clinical Infectious Disease Journal that reported on the detection of several villagers in and around Beijing, China who showed serological evidence of prior infection by H5 and H9 avian viruses.

 

The link to the letter follows:

 

 

Infection With Multiple Avian Influenza Viruses in a Man Without Poultry-Handling Practices Suggesting an Increased Probability of Emergent Pandemic Influenza Virus in General Population

Peng Yang, Weixian Shi, Shujuan Cui, Yi Zhang, Xiujun Liu, and Quanyi Wang

 

The CIDRAP news summary of this letter can be read at the following link:

 

Chinese scientists find evidence of avian flu infection with 2 strains

Chinese researchers identified several villagers who didn't handle poultry to be seropositive for avian flu, including a man who tested seropositive for two strains, according to their letter in Clinical Infectious Diseases yesterday.

 

They conducted a serologic analysis of 605 Beijing-area residents, randomly selected from 24 villages ,who did not have a history of handling poultry. The investigators found antibodies against H9 avian flu by hemagglutination inhibition assay in five of the villagers, and one of these, a 55-year-old man, also tested positive for H5 antibodies.

(Continue . . . )

 

 

Admittedly, these numbers are pretty low.

 

Less than 1% tested positive for prior exposure to H9 avian flu, and only one showed evidence of H5N1 infection.

 

But they do validate that some degree of undetected human infection by these avian influenza viruses have occurred  - and they have happened in the general population - not just in those with frequent poultry exposures.

 

While serological studies like this are rare, we have seen other research over the past couple of years suggesting that both H5N1 and H9N2 have caused silent, or unreported, infections in humans.

 

In September of this year we saw a study that reported the results of this kind of serological testing conducted in a rural village in Thailand in 2008 (see Bangladesh To Share H9N2 Bird Flu Virus). 

 

Out of 800 villagers tested, the authors found 4.7% were seropositive for the Hong Kong H9N2 avian strain, 5.6% had antibodies to A/Thailand/676/2005 H5N1 bird flu, and 3.5% were shown to be seropositive to A/Thailand/384/2006 H5N1 .

 

Last May, in EID Journal: Unraveling Pakistan’s H5N1 Outbreak, we looked at a study that suggested that the actual number of human cases in the 2007 Pakistan cluster was higher than reported.

 

From the abstract, the authors write:

 

Volume 17, Number 6–June 2011

Dispatch

Human Infection with Avian Influenza Virus, Pakistan, 2007

Mukhtiar Zaman, Saadia Ashraf, Nancy A. Dreyer, and Stephen Toovey

Abstract

Human infection with avian influenza (H5N1) virus raises concern for the possibility of a pandemic. We report 20 cases, which ranged from asymptomatic to fatal, in Pakistan in 2007.

 

These cases indicate human-to-human-to-human transmission of this virus, and the number of cases may be higher than realized.

 

In May of 2009 (see Cambodian Study Finds Rare Asymptomatic H5N1 Infections) we saw a seroprevalence study published in the Journal of Infectious Diseases  conducted on more than 600 members of a Cambodian village where 2 human H5N1 cases were detected in 2006.

 

Antibody titers showed that only 1% (7 of 674) of the villagers tested had contracted, and fought off, the H5N1 virus.   A figure much lower than many had expected.

 

Another study – presented at the Options For Influenza Control VI  Conference in Toronto in 2007, came up with similar results (see Seroprevalence Study).

 

So far, all we have are a few ragged pieces of this serological puzzle, gleaned over a period of several years from a handful of countries, and involving extremely small population samples.

 

All of which makes it impossible to draw any firm conclusions.

 

For the glass half-full crowd, these studies do suggest that mild or subclinical infections by these avian viruses – while not particularly common –  can occur. And that may moderate the CFR somewhat.

 

For the glass half-empty contingent, the number of subclinical cases may not be enough to lower the CFR as much as some have hoped, and their detection – even these at low levels – raise concerns over the eventual adaptation of these viruses to humans.

 

What is sorely needed are more detailed serological studies, both among the general population where these viruses are endemic, and among close contacts to known H5N1 and H9N2 infections.

 

But these studies are expensive, difficult to mount due to geographic, societal, political and religious reasons, and are further complicated by the existence of least 20 genetically separate clades of the H5N1 virus, with many minor variants of each clade thrown in the mix.

 

A study conducted where clade 2.3.4 of the H5N1 virus is endemic may not tell us much about subclinical human infections in areas where clade 2.3.2.1 is circulating.

 

 

Without better data, public health officials are forced to make vital decisions regarding the pandemic potential of H5N1, H9N2, and  many other novel viruses based on incomplete information.

 

Which is hardly an enviable position for a world that is unlikely to have much in the way of immunity to a future pandemic caused by one of these emerging influenza strains. 

»» Read More

BMJ Open Study: Self Diagnosis During A Pandemic

 

 

 

Photo Credit CDC Influenza Home Care Guide

 

# 5837

 

We’ve a new study appearing in BMJ Open that looks at just how accurate self diagnosis of influenza during the 2009 pandemic really was.

 

First, a little background.

 

ILIs  . . .  or  Influenza-like Illnesses are among the  most common maladies reported to doctors each year, and while often attributed to `flu’, the causes extend far beyond influenza.

 

The symptoms generally include fever, cough, and body aches  -  but may also commonly include rhinitis, sneezing, headache, fatigue, sore throat, nausea & vomiting, and diarrhea.

 

Influenza A & B, which get most of the headlines, are only responsible for a fraction of the cases of ILI each year. Some estimates put that share as low as 10%.

 

According to the CDC, each year adults (on average) experience 1 to 3 bouts with an ILI, while children may see 3 to 6 flu-like illnesses (cite MMWR)

 

Most of these viral infections are mild, self-limiting, and are almost never identified since testing (beyond, perhaps, a rapid influenza test) is rarely warranted. 

 

Which is why doctors generally refer to ILIs, or Influenza-like Illnesses (or sometimes ARI Acute Respiratory Infection), when making a clinical diagnosis.

 

If an ILI is mild, most people chalk it up to the `common cold’, and if it is more debilitating, figure it is `the flu’.

 

But in reality the spectrum of common respiratory viruses is far more diverse; metapneumovirus, parainfluenzavirus, coronaviruses, respiratory syncytial virus (RSV), enteroviruses, any of the myriad Rhinoviruses  (Common cold), and a number of varieties of adenovirus.

 

 

The prevalence of these non-flu ILI’s complicate the job for doctors and public health officials during a pandemic when limited resources (hospital beds, antivirals, etc) must be prioritized and people must decide whether to go to the ER or self isolate if symptomatic.

 

Which brings us to today’s study, where researchers surveyed more than 1100 people from New Zealand during the 2009 pandemic and compared their perception of whether they caught the flu that year with blood tests showing antibodies to the novel H1N1 virus.

 

 

Self-diagnosis of influenza during a pandemic: a cross-sectional survey

Annemarie Jutel1, Michael G Baker2, James Stanley2, Q Sue Huang3, Don Bandaranayake4

BMJ Open 2011;1:e000234 doi:10.1136/bmjopen-2011-000234

Abstract

Background Self-diagnosis of influenza is an important component of pandemic control and management as it may support self-management practices and reduce visits to healthcare facilities, thus helping contain viral spread. However, little is known about the accuracy of self-diagnosis of influenza, particularly during pandemics.

Methods We used cross-sectional survey data to correlate self-diagnosis of influenza with serological evidence of 2009 pandemic influenza A(H1N1) infection (haemagglutination inhibition titres of ≥1:40) and to determine what symptoms were more likely to be present in accurate self-diagnosis. The sera and risk factor data were collected for the national A(H1N1) seroprevalence survey from November 2009 to March 2010, 3 months after the first pandemic wave in New Zealand (NZ).

Results The samples consisted of 318 children, 413 adults and 423 healthcare workers. The likelihood of being seropositive was no different in those who believed they had influenza from those who believed they did not have influenza in all groups.

Among adults, 23.3% (95% CI 11.9% to 34.7%) of those who reported having had influenza were seropositive for H1N1, but among those reporting no influenza, 21.3% (95% CI 13% to 29.7%) were also seropositive.

Those meeting NZ surveillance or Ministry of Health influenza case definitions were more likely to believe they had the flu (surveillance data adult sample OR 27.1, 95% CI 13.6 to 53.6), but these symptom profiles were not associated with a higher likelihood of H1N1 seropositivity (surveillance data adult sample OR 0.93, 95% CI 0.5 to 1.7).

Conclusions Self-diagnosis does not accurately predict influenza seropositivity. The symptoms promoted by many public health campaigns are linked with self-diagnosis of influenza but not with seropositivity. These findings raise challenges for public health initiatives that depend on accurate self-diagnosis by members of the public and appropriate self-management action.

 

I’ve only printed excerpts from the abstract, but the entire study is open access, and freely available.  The key finding (below) is well illustrated by one of the charts accompanying the study:

 

The likelihood of being seropositive was no different in those who believed they had influenza from those who believed they did not have influenza in all groups.

 

 

In this study, roughly 75% of the people who thought they caught the pandemic flu that fall did not.  While nearly 25% who believed they had not contracted the virus actually had.

 

Even among healthcare workers, the percentage who correctly diagnosed themselves with the pandemic flu was only 33%.

 

And those who reached the conclusion that they had contracted the flu after consultation with a healthcare professional were wrong most of the time as well. 

 

 

Not only can the misidentification of influenza cause serious problems during a pandemic, it also likely skews the public’s perception of the effectiveness of the yearly flu vaccine.

 

Many people complain that in years when they got the shot they still caught the flu. As this study shows, people often mistake non-flu ILIs (which are not covered by the shot) for influenza.

 

The major implication here is that during a pandemic, the majority of people seeking antivirals or medical care due to having flu-like symptoms are likely not to have the pandemic virus.

 

The authors of this study conclude:

 

These findings reinforce public health advice during the pandemic that patients should seek medical care on the basis of disease severity rather than for the purpose of diagnosis.

 

Of course, getting the public to go along with this advice during an influenza pandemic is going to be a lot easier said than done.

»» Read More

PLoS One: H1N1 Seroprevalence Study

 

 

 

#5614

 

 

 

Although relatively mild by pandemic standards, the novel H1N1 virus of 2009 will undoubtedly turn out to be the most studied influenza outbreak in history. Two years after the outbreak began, we continue to see new and sometimes surprising research being published.

 

Today, we’ve a seroprevalence study appearing in PLoS One  that looks at the incidence of infection by the 2009 H1N1 pandemic virus in eastern Scotland during the pandemic.

 

It finds that transmission rates, and number of people infected, was far higher than previously believed; more than 40% of adults tested showed specific antibodies to the pandemic flu.

 

A snippet from the open access study follows, after which I’ll return with more.

 

 

Sero-Prevalence and Incidence of A/H1N1 2009 Influenza Infection in Scotland in Winter 2009–2010

Nigel J. McLeish, Peter Simmonds, Chris Robertson, Ian Handel, Mark McGilchrist, Brajendra K. Singh, Shona Kerr, Margo E. Chase-Topping, Katy Sinka, Mark Bronsvoort, David J. Porteous, William Carman, James McMenamin, Andrew Leigh-Brown, Mark E. J. Woolhouse

(EXCERPTS)

Methods and Findings

We obtained serum samples from a representative sample of 1563 adults resident in Scotland between late October 2009 and April 2010.

 

Based on a microneutralisation assay, we estimate that 44% (95% confidence intervals (CIs): 40–47%) of the adult population of Scotland were sero-positive for A/H1N1 2009 influenza by 1 March 2010.

 

Correcting for background cross-reactivity and for recorded vaccination rates by time and age group, we estimated that 34% (27–42%) were naturally infected with A/H1N1 2009 by 1 March 2010.

 

The central estimate increases to >40% if we allow for imperfect test sensitivity.

<SNIP>

Conclusions

We estimate that almost half the adult population of Scotland were sero-positive for A/H1N1 2009 influenza by early 2010 and that the majority of these individuals (except in the oldest age classes) sero-converted as a result of natural infection with A/H1N1 2009. Public health planning should consider the possibility of higher rates of infection with A/H1N1 2009 influenza in more deprived areas.

 

There is also a press release from the University of Edinburgh, which led this study.

 

Swine flu spread was much wider than first thought, scientists say

The swine flu outbreak of winter 2009-2010 was much more widespread than was previously realized, research suggests

The swine flu outbreak of winter 2009-2010 was much more widespread than was previously realised, research suggests.

 

Blood samples taken from Scottish adults in March last year at the end of the H1N1 flu season showed that almost half were carrying antibodies to the virus.

 

Most of the 44 per cent who tested positive had contracted swine flu, although some had acquired immunity from a previous bout of flu, or had been vaccinated.

 

The research, led by the University of Edinburgh, shows that many cases of swine flu went unreported. Only 100,000 people consulted their GP regarding flu, out of about two million who are believed to have contracted the virus.

 

People living in the most deprived areas were twice as likely to have contracted the virus. Scientists add that it is possible that many people who were vaccinated against the virus were already immune.

(Continue . . . )

 

 

What makes this research particularly interesting is that the attack rate of the H1N1 virus in this study appears to be higher than earlier studies would have suggested. 

 

Last summer, in New Zealand Seroprevalence Study On H1N1, researchers came up with a much lower attack rate (approx. 20%, half asymptomatic).

 

And in late 2009, in UK: H1N1 Serology Tests Reveal Significant Asymptomatic Rate a small study revealed that about 1/3rd of children tested – who were believed more susceptible to the virus than adults – showed antibodies to the virus, while only about 1 in 10 reported flu symptoms.  

 

While we were lucky that this virus produced mild (or even asymptomatic) illness in most cases, the next novel virus to erupt may not be nearly so accommodating. 

 

So research such as this is of more than just academic interest. 

 

It helps to increase our understanding of the attack rates and the patterns of community spread of a novel influenza virus, which should help planners better prepare for the next pandemic.

»» Read More

A Prospective Avian Influenza Transmission Study For Egypt

 

 

 

# 5045

 

 

One of the great mysteries surrounding avian influenza (primarily, but not exclusively H5N1) is how often these viruses jump to and infect humans.   

 

In the relatively short history of our observation of the influenza virus, only the H1, H2, and H3 strains have adapted well to people.  

 

On rare occasions humans have been infected by other influenza strains, such as H5N1, H7N7, and H9N2. These strains are primarily seen in birds, but since they are constantly evolving and mutating, the worry is one might eventually adapt to human hosts.

 

The H5N1 bird flu virus remains at the top of our list of concerns, because it is endemic (in birds) in a number of countries, has shown the rare ability to infect humans, and when it does, it has a incredibly high fatality rate.

 

The two countries reporting the greatest number of human H5N1 cases are Indonesia and Egypt.  The Case fatality rate in Indonesia remains well over 80%, but in Egypt, it runs a much lower (but still disturbing) 32%.

 

Which has led some researchers to wonder if their might be ongoing transmission of a `milder’ or even asymptomatic strain of H5N1 in Egypt.

 

In order to find out, a 3-year seroprevalence study has been designed that would track 1,000 people with various levels of exposure to poultry, and test them regularly for antibodies to the bird flu virus.

 

 

The full details are available at the link below. Here is the abstract.

 

 

 

Prospective study of avian influenza transmission to humans in Egypt

Ghazi Kayali , Richard J Webby , Xiaoping Xiong , Lobna S Sherif , Esmat A El-Ghafar  and Mohamed A Ali

BMC Public Health 2010, 10:685doi:10.1186/1471-2458-10-685

Published:
9 November 2010

Abstract (provisional)

Background

The highly pathogenic avian influenza (HPAI) H5N1 virus remains a public health threat and continues to cause outbreaks among poultry as well as human infections. Since its appearance, the virus has spread to numerous geographic areas and is now considered endemic in Egypt and other countries. Most studies on human H5N1 cases were conducted to investigate outbreak situations and were not designed to address fundamental questions about the epidemiology of human infection with H5N1 viruses. Our objective for this study is to answer these questions by estimating the prevalence and incidence rates of human cases and determine associated risk and protective factors in areas where H5N1 viruses are endemic.

Methods

We designed a 3-year prospective cohort study of 1000 individuals of various exposure levels to poultry in Egypt. At onset, we will collect sera to estimate baseline antibody titers against AI viruses H4-H16. Two follow-up visits are scheduled at 1-year intervals following initial enrollment. At follow-up, we will also collect sera to measure changes in antibody titers over time. Thus, annual prevalence rates as well as incidence rates of infection will be calculated. At each visit, exposure and other data will be collected using a specifically tailored questionnaire. This data will be used to measure risk and protective factors associated with infection. Subjects will be asked to contact the study team any time they have influenza-like illness (ILI). In this case, the study team will verify infection by rapid influenza A test and obtain swabs from the subject's contacts to isolate and characterize viruses causing acute infection.

Discussion

Epidemiologic studies at the influenza human-animal interface are rare, hence many questions concerning transmission, severity, and extent of infection at the population level remain unanswered. We believe that our study will help tackle and clarify some of these issues.

 

 

The few previous seroprevalence studies on H5N1 that we have to date show little or no asymptomatic or mild human infections.

 

Most of these are several years old, however, and are based on older clades of the virus.

 

In May of 2009 (see Cambodian Study Finds Rare Asymptomatic H5N1 Infections) we saw a seroprevalence study published in the Journal of Infectious Diseases  conducted on more than 600 members of a Cambodian village where 2 human H5N1 cases were detected in 2006.

 

Antibody titers showed that only 1% (7 of 674) of the villagers tested had contracted, and fought off, the H5N1 virus.   A figure much lower than many had expected.

 

 

Risk Factors Associated with Subclinical Human Infection with Avian Influenza A (H5N1) Virus—Cambodia, 2006

Sirenda Vong, Sowath Ly, Maria D. Van Kerkhove, Jenna Achenbach, Davun Holl, Philippe Buchy, San Sorn, Heng Seng, Timothy M. Uyeki, Touch Sok, and Jacqueline M. Katz

Abstract-Full Text-PDF Version (175 kB)

 

 

Another study – presented at the Options For Influenza Control VI  Conference in Toronto in 2007, came up with similar results (see Seroprevalence Study).

 

This is how it was reported in MedPage Today .

OPTIONS VI: No Evidence For Mild Avian Flu

By Michael Smith, Senior Staff Writer, MedPage Today

Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.
June 19, 2007

TORONTO, June 18 -- Highly pathogenic avian flu is rarely transmitted to people and apparently never in a mild or asymptomatic form, a Thai researcher said here.

 

A study of 901 people who lived near confirmed victims of the H5N1 avian flu strain showed no serological evidence that they had been infected and fought off the disease, Rapeepan Dejpichai, M.D., of the Thai Ministry of Health told attendees at the Options for Influenza Control meeting.

(Continue . . .)

Given the relative dearth of good seroprevalence studies in the past, this prospective study could go a long way to help answer some very important questions regarding the threat posed by avian influenza viruses to the human population.

»» Read More