EID Journal: Seropositivity For H6 Influenza Viruses In China

Flu Virus binding to Receptor Cells – Credit CDC

 

# 10,011

 

 

In the summer of 2013 Taiwan reported the first known human infection with an avian H6N1 virus, in a a 20-year-old female who was hospitalized with mild pneumonia on the May 8th, treated with oseltamivir (Tamiflu ®), and released from the hospital on the 11th.

 

Were it not for the enhanced surveillance for H7N9, which had only recently broken out in Mainland China, there is a pretty good chance this novel flu infection would have gone unnoticed.

 

And that’s why we really don’t have a good handle on just how often these novel flu viruses jump to humans. Often, these infections present just like any other flu or respiratory infection, and only rarely are the right tests done to determine the cause.

Over the years we’ve seen heated debates and scientific `guesstimates’ that have attempted to quantify the number of people who have been infected with novel H5N1 (see The Great CFR Divide), H3N2v (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012), and H7N9 (see Lancet: Clinical Severity Of Human H7N9 Infection) with varying results.

 

Although difficult to mount, expensive, and subject to some limitations – serological testing of a large cohort of individuals is undoubtedly the best way to determine what the level of exposure to a particular virus a community has experienced.  Infections – even mild or asymptomatic ones – generally leave behind strain-specific antibodies which may be detectable months or even years later.

Assuming your test is sensitive enough to detect the right antibodies, and specific enough not to produce false positives, you can get a pretty good idea how many people in a community have had a previous exposure.  

 

Categorize your test subjects by age, gender, location, and occupation – and you can not only get an idea how common infection with this novel virus is across a population, you can begin to tease out some interesting information about relative exposure risks.

 

Which is exactly what researchers in China have done, looking for evidence of previous H6 influenza exposure among a cross section of people from both Northern and Southern China.  Yesterday, the EID Journal published the following letter, which describes a small, but significant number of people in their serological study who tested positive for H6 influenza antibodies (indicating previous exposure).

 

While the overall number of positives was low (298 by HI, 63 by MN) out of 15,689 samples, not unexpectedly, people with frequent exposure to poultry and/or live birds were more likely to test positive. 

 

Seroprevalence was noticeably higher in the southern provinces than in the north.  Interestingly, this same study found a far lower seropositivity for H5N1 (only 2 positive results), but a much greater seropositivity for H9N2 (3.4% positive).

 

Follow the link below to read this letter, and view its data, in its entirety:

 

Volume 21, Number 7—July 2015

Letter

Seropositivity for Avian Influenza H6 Virus among Humans, China

Li Xin, Tian Bai, Jian Fang Zhou, Yong Kun Chen, Xiao Dan Li, Wen Fei Zhu, Yan Li, Jing Tang, Tao Chen, Kun Qin, Jing Hong Shi, Rong Bao Gao, Da Yan Wang, Ji Ming Chen, and Yue Long Shu

To the Editor: Influenza virus subtype H6 was first isolated from a turkey in 1965 in the United States (1) and was subsequently found in other parts of the world (2). Over the past several decades, the prevalence of H6 virus has dramatically increased in wild and domestic birds (2–4). In China, highly pathogenic influenza A(H5N1), low pathogenicity influenza (H9N2), and H6 are the most prevalent avian influenza viruses among poultry (5). Although only 1 case of H6 virus infection in a human has been reported worldwide (6), several biological characteristics of H6 viruses indicate that they are highly infectious to mammals. Approximately 34% of H6 viruses circulating in China have enhanced affinity to human-like receptors (ɑ-2,6 NeuAcGal) (2). H6 viruses can also infect mice without prior adaptation (2,7), and some H6 viruses can be transmitted efficiently among guinea pigs (2). To evaluate the potential threat of H6 viruses to human health, we conducted a systematic serologic study in populations occupationally exposed to H6 viruses.

During 2009–2011, a total of 15,689 serum samples were collected from live poultry market workers, backyard poultry farmers, large-scale poultry farmers, poultry-slaughter factory workers, and wild bird habitat workers in 22 provinces in mainland China. A/chicken/Y94/Guangdong/2011 (H6N2), a representative isolate of predominant H6 viruses in mainland China, was used for the serologic testing (Technical Appendix[PDF - 155 KB - 4 pages] Table 1). Hemagglutination inhibition (HI) assay was performed for all serum samples, and samples with an HI titer ≥20 were verified by a microneutralization (MN) assay, as indicated by World Health Organization guidelines (8). An MN result of ≥20 was considered positive.

The HI result was ≥20 for H6N2 virus in 298 of the 15,689 specimens, and the MN result was positive in 63 of the 298 specimens (overall seropositivity range 20–320, mean 32.7, 0.4%) (Technical Appendix[PDF - 155 KB - 4 pages] Table 2). The proportion of group members who were seropositive differed significantly according to occupational exposure (p = 0.0125). Seropositivity was highest among workers in live poultry markets, backyard poultry farmers, and workers in wild bird habitats (s0.66%, 0.42%, and 0.51%, respectively) (Table). According to χ² test results, seropositivity among workers in live poultry markets was significantly higher than that among large-scale poultry farmers (p = 0.0015, adjusted ɑ = 0.005. Analysis by unconditional logistic regression model showed that exposure to live poultry markets was a risk factor for human infection with avian influenza H6 virus (odds ratio 2.1, 95% CI 1.27–3.47).

Seropositivity did not differ significantly among male and female persons tested (p = 0.08) (Table). No children were positive for the H6N2 virus. For other age groups, seropositivity ranged from 0.25% to 0.45%, but differences were not significant (p>0.05) (Table).

Of the 22 provinces from which serum specimens were collected, 11 were northern provinces and 11 were southern provinces. Positive specimens were detected in all southern provinces. In northern China, no seropositive results were detected in Henan, Liaoning, or Jilin Provinces. According to χ² test results, seropositivity in southern China was significantly higher than seropositivity in northern China (p = 0.0375) (Table).

Human infection with influenza H6 virus in mainland China has not been reported, but 63 serum specimens tested in our study were positive for the H6 virus. This level of seropositivity is much higher than that for highly pathogenic avian influenza A(H5N1) virus, for which only 2 of the serum specimens we tested were positive (data not shown), but much lower than the seropositivity level for low pathogenicity avian influenza A(H9N2) virus; 3.4% of the samples tested were positive for A/Chicken/Hong Kong/G9/1997(H9N2)–like virus (data not shown). A previous US study has reported H6N2-positive antibodies in veterinarians (9). Our results and the veterinarian study indicate that the H6N2 virus could infect humans.

In our study, positive samples were detected in 19 of 22 provinces and in all tested worker populations, suggesting that the H6 virus has been broadly circulating in birds in China. Live poultry market exposure is the major risk factor for human infection with avian influenza H6 virus. The limitation of this study is that antigen selection may not accurately detect neutralization antibodies for different subtypes of H6 viruses. Surveillance of the H6 virus in birds and occupationally exposed populations should be strengthened for pandemic preparedness.

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Seroprevalence Of Influenza Viruses In Cats - China

 

 

# 9893

 

Up until a dozen years ago, most veterinarians would have told you that cats (and dogs) are not generally susceptible to human influenza viruses.  That notion began to change in 2004, when we saw  two unrelated events; the jump of equine H3N8 influenza from horses to Florida greyhounds, and the infection of more than 100 tigers by avian H5N1 in Thailand.

 

Just six weeks ago we saw history repeat itself, with the announcement from the Guangxi Zoo: Reports 2 Tiger Deaths Due To H5N1.

 

Although poultry and pigs get most of our attention, over the past decade we’ve a growing body of evidence confirming a wide spectrum of influenza carriage by both dogs and cats.  A few examples include:

• In 2006, Dr. C.A. Nidom demonstrated that of 500 cats he tested in and around Jakarta, 20% had antibodies for the H5N1 bird flu virus. 
• Findings that prompted the FAO in 2007 to warned that: Avian influenza in cats should be closely monitored,
• In 2008 the CDC’s EID Journal carried a report on a newly emerging canine flu in Korea jumping from an avian source (see Transmission of Avian Influenza Virus (H3N2) to Dogs).
• In 2011, we saw the plot thicken yet again, when it was announced that this canine H3N2 had jumped to cats (see Korea: Interspecies Transmission of Canine H3N2). 
• And during the 2009 H1N1 pandemic, we saw cases of reverse zoonosis, where dogs (and cats) contracted the `humanized’ H1N1 virus from their human contacts (see US: Dog Tests Positive For H1N1)
• In 2012 the OIE reported on Cats Infected With H5N1 in Israel, although so far no sustained virus transmission in cats or from cats to humans has been observed.
• Dogs have also been found to be susceptible to (apparently asymptomatic) infection with the recently emerged H5N8 virus (see MAFRA: H5N8 Antibodies Detected In South Korean Dogs (Again).
• Companion animals like dogs and cats are increasingly being viewed as potential `mixing vessels’  for influenza reassortment (see Study: Dogs As Potential `Mixing Vessels’ For Influenza).

 

In late 2012, in China: Avian-Origin Canine H3N2 Prevalence In Farmed Dogs, we saw a study that found more than 12% of farmed dogs tested in Guangdong province carried a strain of canine H3N2 similar to that seen in Korea.  The authors cautioned:

As H3N2 outbreaks among dogs continue in the Guangdong province (located very close to Hong Kong), the areas where is densely populated and with frequent animal trade, there is a continued risk for pets H3N2 CIV infections and for mutations or genetic reassortment leading to new virus strains with increased transmissibility among dogs.

Further in-depth study is required as the H3N2 CIV has been established in different dog populations and posed potential threat to public health.

 

Today, in a similar vein, we’ve a study out of China that looks at the seroprevalence of (avian origin) canine H3N2, along with two seasonal human flu viruses, in cats in Northern China.

 

Serological survey of canine H3N2, pandemic H1N1/09, and human seasonal H3N2 influenza viruses in cats in northern China, 2010–2014

Xuxiao Zhang^†, Ye Shen^†, Lijie Du, Ran Wang, Bo Jiang, Honglei Sun, Juan Pu, Degui Lin, Ming Wang, Jinhua Liu and Yipeng Sun^*

Virology Journal 2015, 12:50  doi:10.1186/s12985-015-0285-5

Published: 1 April 2015

Abstract (provisional)

Background The close contact between cats and humans poses a threat to public health because of the potential zoonotic transmission of influenza viruses to humans. Therefore, we examined the seroprevalence of pandemic H1N1/09, canine H3N2, and human H3N2 viruses in pet cats in northern China from 2010 to 2014.

Finding Of 1794 serum samples, the seropositivity rates for H1N1/09, canine H3N2, and human H3N2 were 5.7%, 0.7%, and 0.4%, respectively. The seropositivity rate for H1N1/09 in cats was highest in 2010 (8.3%), and then declined continuously thereafter. Cats older than 10 years were most commonly seropositive for the H1N1/09 virus.

Conclusions Our findings emphasize the need for continuous surveillance of influenza viruses in cats in China.

(EXCERPT)

Different subtypes of influenza viruses are reported to be naturally transmitted to cats from other species worldwide, including avian viruses (H5N1), canine viruses (H3N2), and human viruses (pandemic H1N1/09, seasonal H1N1, and H3N2) [1-3]. The close contact between cats and humans possesses a threat to public health because of the potential zoonotic transmission of influenza viruses to humans. In China, the canine H3N2 and H1N1/09 influenza viruses circulate in dogs [4], and the seasonal H3N2 and H1N1/09 viruses are prevalent in humans [5,6], any of which might be transmitted to cats. Therefore, we examined the seroprevalence of the pandemic H1N1/09, canine H3N2, and human seasonal H3N2 influenza viruses in cats in northern China from January 2010 to June 2014.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

 

 

For a virus, successfully jumping to a new species is akin to hitting the lottery. A fresh supply of hosts not only increases its odds of long-term survival, it may also provide new opportunities for evolution and/or reassortment with other viruses.

 

Last summer, in Canine H3N2 Reassortant With pH1N1 Matrix Gene, we looked at exactly that scenario, in a report appearing in the journal Epidemiology & Infection, that found a new reassortment of the canine H3N2 virus – one that has picked up the M (matrix) gene from the 2009 H1N1 pandemic virus.

 

If this sounds vaguely familiar, it is because we’ve seen this same M gene showing up regularly in all three North American swine variant viruses (H1N1v, H1N2v, H3N2v), which caused more than 300 human infections to be reported in 2012. The CDC has speculated that:

`This M gene may confer increased transmissibility to and among humans, compared to other variant influenza viruses.’ – CDC HAN 2012

 

Whether any of this means that canine H3N2 is on the fast track towards `humanization’ is anyone’s guess, but this does illustrate just how intertwined avian, canine, and human influenza viruses really are.

 

Something that the American Society for Microbiology warned about last summer, in a press release on a study of canine influenza viruses:

Evolution of Equine Influenza Led to Canine Offshoot Which Could Mix With Human Influenza

CONTACT:  Jim Sliwa
jsliwa@asmusa.org

WASHINGTON, DC – June 19, 2014 – Equine influenza viruses from the early 2000s can easily infect the respiratory tracts of dogs, while those from the 1960s are only barely able to, according to research published ahead of print in the Journal of Virology. The research also suggests that canine and human influenza viruses can mix, and generate new influenza viruses.

(Continue . . . )

 

All of which highlights the importance of continued surveillance – and not just of pigs and poultry – for emerging novel influenza viruses all over the world.

BMC: H10N8 Antibodies In Animal Workers – Guangdong Province, China

Credit FAO

 

# 9255

 

Avian H10 viruses haven’t garnered a lot of attention until relatively recently, as they rarely produce symptoms in poultry, and human infections have been both rare, and mild.  All of that changed last winter when China reported three fatal H10N8 infections (see Jiangxi Province Reports 3rd H10N8 Case) in quick succession.

LPAI (Low Path Avian Influenza) H10N8 had been previously reported in a duck sampled back in 2012 from Guangdong province, but was otherwise not well described. 

Human infections with a close cousin – H10N7 – had previously been reported in two children in Egypt in 2004 (see Avian Influenza Virus A (H10N7) Circulating among Humans in Egypt) and among abattoir workers in Australia in 2012 (see EID Journal: Human Infection With H10N7 Avian Influenza).  

 

In both cases illness was described as mild, and of short duration.

 

A side note, we also looked at a recent outbreak of H10N7 in European seals (see Avian H10N7 Linked To Dead European Seals), with warnings to the public to avoid contact.

Since testing for novel flu viruses among humans is only very rarely done, we don’t have a good handle on how often these `oddball’ avian flu viruses actually jump to humans. 

 

While probably fairly rare – and largely restricted to those who have a lot of contact with wild or domesticated birds – it is is likely more common than we might otherwise think. For more on prior research on seroprevalence of other rare avian influenzas see A Little Background On H11 Avian Influenzas.

 

In any event, the 2012 detection of H10N8 in a Guangdong duck, followed last year by the infection and deaths of three people from this emerging virus, inspired a group of Chinese scientists go to back and test hundreds of archived blood samples taken prior to the first known human case, to look for signs of previous H10N8 infection.

 

Although the seroprevalence for this virus appears very low, out of 827 sera tested  they found 21 mildly reactive , with three showing titers of  at least 1:40.  One, with an MN antibody titer of 1:80, was strongly suggestive of prior infection.  With this baseline, future seroprevalence studies of animal workers might provide an indirect early warning system, should this virus continue to spread stealthily in the poultry population.

The study appears in BMC Medicine. (Note there appears to be a temporary problem with the link)

 

Antibodies against H10N8 Avian Influenza Virus among Animal Workers in Guangdong Province before November 30, 2013, the First Recognized Human H10N8 Case

BMC Medicine 2014, 12:205 doi:10.1186/s12916-014-0205-3

Wenbao Qi, Shuo Su , Chencheng Xiao, Pei Zhou, Huanan Li, Changwen Ke , Gregory C Gray, Guihong Zhang , Ming Liao 

Abstract

Background
Considered an epicenter of pandemic influenza virus generation, southern China has recently seen an increasing number of human H7N9 infections. However, it is not the only threat. On 30 November 2013, a human H10N8 infection case was first described in China. The origin and genetic diversity of this novel virus is similar to that of H7N9 virus. As H10N8 avian influenza virus (AIV) was first identified from a duck in Guangdong Province during 2012 and there is also evidence of H10N8 infected dogs in this region, we sought to examine archived sera from animal workers to see if there was evidence of subclinical human infections before the first human H10N8 cases.

Methods

We studied archived serum samples (cross-sectional study, convenience sample) collected between May and September 2013 from 710 animal workers and 107 non-animal exposed volunteers living in five cities of Guangdong Province. Study participants’ sera were tested by horse red blood cells (RBCs) hemagglutination inhibition (HI) and microneutralization (MN) assays according to World Health Organization guidelines. The A/Jiangxi-Donghu/346-1/2013(H10N8) virus was used. Sera which have an HI assay ≥1:20 were further tested with the MN assay. Questionnaire data were examined for risk factor associations with positive serological assays. Risk factor analyses failed to identify specific factors associated with probable H10N8 infections.

Results

Among the 827 sera, only 21 animal workers had an HI titer ≥1:20 (18 had an HI titer of 1:20 and 3 had an HI titer of 1:40). None of these 21 subjects reported experiencing any influenza symptoms during the three months before enrollment. Among the three subjects with HI titers of 1:40, two had MN antibody titers of 1:40, and one had a MN antibody titer of 1:80 (probable H10N8 infections).

Conclusions

Study data suggest that animal workers may have been infected with the H10N8 virus before the first recognized H10N8 human infection cases. It seems prudent to continue surveillance or H10N8 viruses among animal workers.

 

EID Journal: Three Decades Of MERS-CoV Antibodies In Camels

Credit FAO

 

 

# 8957

 

 

Although it certainly seems longer, it has been just over a year since we saw the first real evidence linking camels to the MERS-CoV virus (see Lancet: Camels Found With Antibodies To MERS-CoV-Like Virus).  Since then, as testing procedures have matured and been deployed, we’ve seen a steady stream of studies showing that many Middle Eastern dromedaries either carry the live virus, or antibodies indicating prior infection.

 

mBio: Airborne Fragments Of MERS-CoV Detected In Saudi Camel Barn

Eurosurveillance: MERS-CoV Antibodies & RNA In Camel’s Milk – Qatar

Kuwait Tests Camels - Finds 6% Positive For MERS-CoV

mBio: MERS-CoV Carriage By Dromedaries

 

While bats are still a prime suspect as the reservoir host for this emerging coronavirus, camels increasingly are viewed as an important intermediate host, and possible bridge to infecting humans (see WHO Update On MERS-CoV Transmission Risks From Animals To Humans & FAO: `Stepped Up’ Investigations Into Role Of Camels In MERS-CoV).

 

While human cases have only originated on the Arabian peninsula, that region imports tens of thousands of camels each year from the Horn of Africa, leading some to suspect the actual `source’ of the MERS coronavirus might come from the East African nations of Somalia, Kenya, or Sudan. 

 

Last May, in  EID Journal: MERS Antibodies In Camels – Kenya 1992-2013, we saw a study using archived camel blood samples going back 20 years that found MERS antibodies were circulating in Kenya as early as 1992.  Today, we’ve a new study that pushes back the clock at least another 10 years.

Volume 20, Number 12—December 2014

Dispatch

MERS Coronavirus Neutralizing Antibodies in Camels, Eastern Africa, 1983–1997

Marcel A. Müller¹ , Victor Max Corman¹, Joerg Jores, Benjamin Meyer, Mario Younan, Anne Liljander, Berend-Jan Bosch, Erik Lattwein, Mosaad Hilali, Bakri E. Musa, Set Bornstein, and Christian Drosten

Abstract

To analyze the distribution of Middle East respiratory syndrome coronavirus (MERS-CoV)–seropositive dromedary camels in eastern Africa, we tested 189 archived serum samples accumulated during the past 30 years. We identified MERS-CoV neutralizing antibodies in 81.0% of samples from the main camel-exporting countries, Sudan and Somalia, suggesting long-term virus circulation in these animals.

(Continue . . .)

 

You’ll want to read the entire paper for methods, materials, and their detailed findings.  In the conclusion, the authors write:

 

MERS-CoV sequences from camels in Saudi Arabia and Qatar were closely related to sequences found in humans and did not show major genetic variability that would support long-term evolution of MERS-CoV in camels (10,11). The MERS-CoV sequence from a camel in Egypt was phylogenetically most distantly related to all other known camel-associated MERS-CoVs but closely related to the early human MERS-CoV isolates (10). An urgent task would be to characterize the diversity of MERS-related CoV in other camels in Africa to elucidate whether the current epidemic MERS-CoV strains have evolved toward more efficient human transmissibility.

The existence of unrecognized human infections in African or Arabian countries in the past cannot be ruled out. Resource-limited African countries that have been exposed to civil unrest, such as Somalia and Sudan, are not likely to diagnose and report diagnostically challenging infections resembling other diseases. The lack of MERS-CoV antibodies in a small cohort serosurvey in Saudi Arabia did not suggest the long-term circulation of MERS-CoV in humans on the Arabian Peninsula (15).

Large serosurveys in countries where camels are bred and traded, especially in eastern Africa, are needed to explore the general MERS-CoV seroprevalence in camels and humans, particularly humans who have close contact with camels. Such serosurveys could provide the data needed to ascertain whether MERS-CoV has been introduced into, but unrecognized in, the human population on the African continent.

BMC: Decline Of Antibody Titers With A(H1N1)pdm Over Time

Credit NIAID

 

 

# 8875

 

The arrival of a novel H1N1 influenza pandemic virus in 2009 – the first one in more than 40 years – has provided researchers with unique opportunities to observe how a newly introduced flu virus behaves in humans, and quite frankly, in other species as well (see The 2009 H1N1 Virus Expands Its Host Range (Again)).

 

Serological studies that would have been impractical before on H3N2 or the old seasonal H1N1 virus – due to decades of ongoing exposure to these strains – suddenly became possible with a new flu in town.

 

One of the unanswered questions surrounding our immune response to influenza infection is how long does our acquired immunity last?  

 

Admittedly, the answer to that question will vary from one person to the next, and depend on a variety of factors including the strain of flu, the person’s age, general health, and state of their immune system.  And there seems to be a difference between the duration of immunity gained from actual infection vs. through vaccination.

 

Despite circulating now for more than 5 years, the (now seasonal) H1N1 virus remains antigenically very similar to the pandemic strain that emerged in the spring of 2009.  So much so that an an A/California/7/2009 (H1N1)pdm09-like virus will be used for the sixth year running in the flu vaccine. 

Yet, despite having a half of decade of vaccination and natural exposure to this new H1N1 virus, last year saw a particularly heavy H1N1 flu season in North America. Normally, we’d look to antigenic drift to explain a major resurgence of a seasonal flu virus after several years, but H1N1 has been remarkably (albeit, not totally) stable in that regard.

   

Drift is the standard evolutionary path of influenza viruses, and comes about due to replication errors that are common with single-strand RNA viruses (see NIAID Video: Antigenic Drift) Drift is primarily responsible for the need to change flu vaccine strains every couple of years (something that is yet to happen with H1N1).

 

Another possibility is waning immunity, something that is recognized (particularly with vaccines, and among the elderly), but has been difficult to quantify in the past.  Given the immune system’s tabula rasa with regards to the 2009 H1N1 virus, it has become possible to track the decline of antibody titers of a cohort of individuals who were first exposed five years ago.

 

Rate of decline of antibody titers to pandemic influenza A (H1N1-2009) by hemagglutination inhibition and virus microneutralization assays in a cohort of seroconverting adults in Singapore

Jung Pu Hsu, Xiahong Zhao, Mark I-Cheng, Alex R Cook, Vernon Lee, Wei Yen Lim, Linda Tan, Ian G Barr, Lili Jiang, Chyi Lin Tan, Meng Chee Phoon, Lin Cui, Raymond Lin, Yee Sin Leo and Vincent T Chow

BMC Infectious Diseases 2014, 14:414  doi:10.1186/1471-2334-14-414

Published: 28 July 2014

Abstract (provisional)

Background

The rate of decline of antibody titers to influenza following infection can affect results of serological surveys, and may explain re-infection and recurrent epidemics by the same strain.

Methods

We followed up a cohort who seroconverted on hemagglutination inhibition (HI) antibody titers (>=4-fold increase) to pandemic influenza A(H1N1)pdm09 during a seroincidence study in 2009. Along with the pre-epidemic sample, and the sample from 2009 with the highest HI titer between August and October 2009 (A), two additional blood samples obtained in April 2010 and September 2010 (B and C) were assayed for antibodies to A(H1N1)pdm09 by both HI and virus microneutralization (MN) assays. We analyzed pair-wise mean-fold change in titers and the proportion with HI titers >= 40 and MN >= 160 (which correlated with a HI titer of 40 in our assays) at the 3 time-points following seroconversion.

Results

A total of 67 participants contributed 3 samples each. From the highest HI titer in 2009 to the last sample in 2010, 2 participants showed increase in titers (by HI and MN), while 63 (94%) and 49 (73%) had reduction in HI and MN titers, respectively.

Titers by both assays decreased significantly; while 70.8% and 72.3% of subjects had titers of >= 40 and >= 160 by HI and MN in 2009, these percentages decreased to 13.9% and 36.9% by September 2010. In 6 participants aged 55 years and older, the decrease was significantly greater than in those aged below 55, so that none of the elderly had HI titers >= 40 nor MN titers >= 160 by the final sample.

Due to this decline in titers, only 23 (35%) of the 65 participants who seroconverted on HI in sample A were found to seroconvert between the pre-epidemic sample and sample C, compared to 53 (90%) of the 59 who seroconverted on MN on Sample A.

Conclusions

We observed marked reduction in titers 1 year after seroconversion by HI, and to a lesser extent by MN. Our findings have implications for re-infections, recurrent epidemics, vaccination strategies, and for cohort studies measuring infection rates by seroconversion.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

 

The entire study is available, and well worth reading, but I’ve excerpted two paragraphs below that sum up their findings.  

Discussion

The objective of our study was to understand temporal changes in antibody titers following seroconversion during the initial epidemic of A(H1N1)pdm09 infections in  Singapore. Our results revealed a fairly rapid decline in antibody titers following seroconversion, with only a fifth of those who originally had HI titers of  ≥40 and half of those with MN titers of  ≥160 still  having  titers  above  the  respective  cut-off  points  after  a  year.  There  was  also  some indication  that  the  rate  of  decline  was  higher  in  older  individuals,  and  that  the  change  in antibody  titers  measured  by  HI  was  greater  than  by  MN.  Symptomatic  infections  were associated with higher starting antibody titers, and continued to have marginally higher titers in subsequent samples, at least by MN assays.

<SNIP>

Conclusions

Six  months  and  one  year  after  antibodies  peaked  following  presumptive  infection  with A(H1N1)pdm09, only 25% and 14% of participants respectively had antibody  titers against A(H1N1)pdm09 that would be considered protective (HI titer ≥40). The decline in antibody titers may explain susceptibility to re-infections, and recurrent epidemics following the initial epidemic of infections during the pandemic. It also suggests that influenza vaccination may have to be administered more frequently in the tropics where there is year-round circulation of influenza viruses. The rate of decline in elderly individuals may be even more rapid, and if our  findings  are  confirmed,  may  necessitate  alternative  strategies  of  influenza  vaccine development for this vulnerable group.

 

 

A pretty good reminder that even if you got the vaccine last year – or worse, endured the flu last winter – you may not be carrying sufficient immunity forward into the new flu season to protect you against re-infection. 

 

And given that H3N2, and two lineages of Influenza B, are also in circulation – your risks of catching some kind of flu are compounded further.

 

Which is why, even though the H1N1 component of the flu vaccine remains unchanged this year, it is a good idea to get the flu vaccine every year.  

 

Despite variable and sometimes disappointing VE (Vaccine Effectiveness) numbers (see CIDRAP: A Comprehensive Flu Vaccine Effectiveness Meta-Analysis) - particularly among the elderly (see BMC Infectious Diseases: Waning Flu Vaccine Protection In the Elderly) - we continue to see evidence of substantial benefit from the flu shot.

 

For more, you may wish to revisit:

 

CDC: Flu Shots Reduce Hospitalizations In The Elderly

Research: Low Vaccination Rates Among 2013-2014 ICU Flu Admissions

Two Studies On The 2009 Pandemic Flu Vaccine & Pregnancy

EID Journal: Two Dispatches On SFTS

Photo Credit Wikipedia

Tick Species Associated with SFTS in China

# 8804

 

 

SFTS or Severe Fever with Thrombocytopenia Syndrome - a tickborne Phlebovirus  - was first discovered in China in 2009, but has also been found in Japan and Korea. It is genetically similar to the recently discovered Heartland Virus (see MMWR: Heartland Virus Disease — United States, 2012–2013) that has been detected in roughly a dozen people here in the United States.

 

Phleboviruses are part of the very large family Bunyaviridae.

 

To date over three hundred Bunyaviruses have been identified around the world, with rodents often cited as carriers. While not all Bunyaviruses are dangerous to humans (some only infect plants), the Bunyavirus family include such nasties as Crimean-Congo hemorrhagic fever (CCHF), Hantaviruses, and Rift Valley Fever.

 

Most are spread via arthropod vectors (ticks, mosquitoes & sand flies), with the notable exception of Hantaviruses (see Hantaviruses Revisited), which are primarily spread via virus-laden feces and urine of rodents.

 

In 2011, we got our first good look at the disease when the NEJM published a study Fever with Thrombocytopenia Associated with a Novel Bunyavirus in China.  STFS has previously been associated with a 12% mortality rate in China. Since then we’ve seen reports both from Japan and South Korea (see Korean CDC On SFTS Cases) of fatal cases as well.

 

Like with CCHF, under the right conditions, human-to-human transmission of SFTS (via blood, mucus or other bodily fluids) has been documented. (see Person-to-person transmission of severe fever with thrombocytopenia Syndrome virus)

 

As a relatively newly discovered pathogen, we are just beginning to learn about its prevalence, both in ticks and in humans in SFTS endemic areas.  

 

Today, we’ve excerpts from two dispatches published in the CDC’s EID Journal that help in that regard.

 

The first, looks at the various species and the rate of SFTS infection among ticks collected South Korean. They found SFTSV in 5.7% of H. longicornis ticks tested, which represented 81.2% of the ticks sampled.  Other species tested were also found to carry the virus, but it isn’t yet known whether they can transmit it to humans. 

 

Severe Fever with Thrombocytopenia Syndrome Virus in Ticks Collected from Humans, South Korea, 2013

Seok-Min Yun¹, Wook-Gyo Lee¹, Jungsang Ryou, Sung-Chan Yang, Sun-Whan Park, Jong Yeol Roh, Ye-Ji Lee, Chan Park, and Myung Guk Han

Author affiliations: Korea Centers for Disease Control and Prevention, Cheongwon-gun, South Korea

Abstract

We investigated the infection rate for severe fever with thrombocytopenia syndrome virus (SFTSV) among ticks collected from humans during May–October 2013 in South Korea. Haemaphysalis longicornis ticks have been considered the SFTSV vector. However, we detected the virus in H. longicornis, Amblyomma testudinarium, and Ixodes nipponensis ticks, indicating additional potential SFTSV vectors.

 

The second study, this time out of China, is a seroprevalence study of healthy individuals, looking for evidence of prior infection with SFTS, without a history of severe illness. 

 

Antibodies against Severe Fever with Thrombocytopenia Syndrome Virus in Healthy Persons, China, 2013

Lei Zhang¹, Jimin Sun¹, Jie Yan, Huakun Lv, Chengliang Chai, Yi Sun, Bin Shao, Jianmin Jiang, Zhiping Chen, and Yanjun Zhang

Abstract

In June 2013, a subclinical infection with severe fever with thrombocytopenia syndrome virus (SFTSV) was detected in Zhejiang Province, China, prompting seroprevalence studies in 6 districts within the province. Of 986 healthy persons tested, 71 had IgG antibodies against SFTSV. This finding suggests that most natural infections with SFTSV are mild or subclinical.

Conclusions

SFTSV can cause severe disease and high rates of death among infected hospitalized patients. The virus also has the limited ability to be transmited from person to person through contact with contaminated blood, but secondary cases are generally less severe and have so far not resulted in fatalities (7–9). Nonetheless, there is great public health concern regarding SFTSV.

Our seroprevalence study was prompted by the identification of a subclinical, secondary infection that was most likely caused by person-to-person transmission of the virus from an infected family member with a fatal case of SFTS. We found an overall SFTSV seroprevalence of 7.2% among 986 healthy persons who reported no symptoms associated with SFTS. Because the seropositive participants in our study did not have contact with persons with diagnosed cases of SFTS, their infections most likely occurred through natural exposure. From this, we conclude that SFTSV infections are widespread in rural areas of Zhejiang Province, and only a small percentage of the infections result in clinical disease.

 

Like a lot of viruses, infection with SFTS appears to carry with it a wide range of illness – ranging from subclinical to mild to occasionally life-threatening.  Very few viruses are universally fatal (rabies comes close, though).

 

This is a pattern we see with everything from influenza to West Nile Virus to MERS. It is also a fact of life that surveillance is far more likely to pick up severe cases than mild ones, and that can sometimes skew our perception of just how deadly an emerging pathogen really is.

 

You don’t have to travel to Asia to be exposed to a potentially serious  tickborne disease.  The CDC maintains a long  (and growing) list of of tickborne pathogens available locally, including:

 

Babesiosis , Ehrlichiosis, Lyme disease, Rickettsia parkeri Rickettsiosis, Rocky Mountain Spotted Fever (RMSF), STARI (Southern Tick-Associated Rash Illness), Tickborne relapsing fever (TBRF), Tularemia, and 364D Rickettsiosis.

 

Whether a new and emerging threat, or simply our ability to finally recognize a long-time nemesis, it makes sense to take precautions against ticks and other vector-borne diseases.

 

For help in that regard, the following CDC website offers advice on:

 

Preventing Tick Bites

 

And for more on tickborne pathogens, you may wish to revisit:

 

EID Journal: Seroprevalence Of B. Miyamotoi In N.E. United States

The Tick Borne Identity

CDC: Estimate Of Yearly Lyme Disease Diagnoses In The United States

EID Journal: MERS Antibodies In Camels – Kenya 1992-2013

Photo Credit Wikipedia

 

# 8579

 

Adding to the list of studies (see here, here, & here) that have found evidence of MERS coronavirus infection in dromedary camels across a wide swath of the Middle East (including Oman, Saudi Arabia, the UAE, Jordan, Qatar, Spain, and Egypt) we now have a study conducted on camels from Kenya, a region that exports many animals to the Arabian peninsula and Egypt for slaughter.

 

The authors tested blood samples taken from farmed or nomadic camels and archived serum samples obtained from the International Livestock and Research Institute (ILRI) (Nairobi, Kenya).

 

Of 774 dromedaries tested, a total of 228 (29.5%) were rated MERS-CoV positive by the rELISA testing. Younger camels were shown to have the lowest levels of antibodies, and are most likely to carry the live virus. 

 

Given that few camels are exported from the Arabian peninsula to the horn of Africa, the finding of high levels of MERS antibodies in East African dromedaries may suggest local acquisition of the virus.  A finding that may lead to a better understanding of the natural ecology and history of the MERS coronavirus.

 

 

Dispatch

Antibodies against MERS Coronavirus in Dromedary Camels, Kenya, 1992–2013

Article Contents

Victor M. Corman¹, Joerg Jores¹, Benjamin Meyer¹, Mario Younan, Anne Liljander, Mohammed Y. Said, Ilona Gluecks, Erik Lattwein, Berend-Jan Bosch, Jan Felix Drexler, Set Bornstein, Christian Drosten , and Marcel A. Müller

Abstract

Dromedary camels are a putative source for human infections with Middle East respiratory syndrome coronavirus. We showed that camels sampled in different regions in Kenya during 1992–2013 have antibodies against this virus. High densities of camel populations correlated with increased seropositivity and might be a factor in predicting long-term virus maintenance.

(Continue . . . )

 

The materials and methods section of the dispatch is lengthy and detailed, and will be of most interest to researchers, so I’ve skipped ahead to their wrap up:

 

Conclusions

The present study showed that dromedary camels from Kenya have antibodies against MERS-CoV, which complements the current finding that MERS-CoV is a common pathogen in dromedary camel populations (5,6,8,9,13). Our finding of MERS-CoV antibodies in dromedary camels as early as 1992 is consistent with findings of a recent report from Saudi Arabia, which suggested that MERS-CoV has been circulating in dromedary camels for ≥20 years (5).

To project and potentially control virus spread, the public health community must understand factors determining virus maintenance. Our group and others have demonstrated that young dromedary camels have lower seroprevalences and are more likely to carry infectious virus (5,6). Similar observations have been made for coronaviruses in their original chiropteran hosts wherein strong virus amplification occurred soon after the time of parturition (15). Young, immunologically naive animals may thus facilitate virus amplification in dromedary camel populations.

We also demonstrated that dromedary camel population density shows a positive correlation with MERS-CoV seropositivity, which suggests efficient MERS-CoV maintenance or spread if herd density is high. Different types of animal husbandry in the Northeastern and Eastern regions of Kenya might be better predictors of virus transmission among camels. Dromedary camels in this area are often nomadic following rainfall patterns, and are taken across borders into neighboring countries, such as Ethiopia, for trade purposes (13). The observed increase in seropositivity from the Western region to the Northeastern and Eastern regions could be attributed to increased animal-to-animal contact in cross-border dromedary camel metapopulations.

Conversely, dromedary camels that originated in the Northeastern region but had been held in isolation since 1998 were negative for MERS-CoV antibodies, which is consistent with absence of antibodies in dromedary camels bred in isolation in Dubai (6). The combination of nomadic husbandry for a large population and presence of young virus-susceptible animals might facilitate virus maintenance. However, our retrospective study with archived samples could not assess hypotheses for each of the individual variables to determine their relative and absolute degrees of influence on virus circulation.

Because exportation of dromedary camels is largely unidirectional from eastern Africa into the Arabian Peninsula (11), our findings might facilitate the search for more ancestral MERS-CoV variants to clarify the natural history of acquisition of MERS-CoV by dromedary camels and its putative transmission to humans. Our recent finding of a MERS-CoV ancestor in bats from South Africa (3) highlights the need for wider investigations of viral reservoirs. The fact that no human MERS cases have been observed in eastern Africa could indicate less transmissibility of viruses in regional lineages or lack of detection and reporting of cases. Serosurveys of persons handling dromedary camels in this region could help to determine whether silent or unrecognized infections are being maintained in humans.

Referral: VDU Blog- Can we believe every H7N9 seroprevalence study we see?

 

# 8431

 

While Dr. Ian Mackay is taking a well deserved (but hopefully brief) blogging break, guest blogger @influenza_bio has penned an absolutely terrific piece on how seroprevalence studies are conducted, and how they can sometimes go wrong. 

I’ll not spoil this beyond saying that - not only do I now know a whole lot more about seroprevalence studies than ever before -  I’ve converted this essay into a PDF file, and it now sits on my desktop for future reference. 

 

By all means, get out of here and go read:

 

Friday, 4 April 2014

Can we believe every H7N9 seroprevalence study we see?

Special Guest writer: @influenza_bio

 

Highly Recommended.

Lancet: Community Burden & Severity Of Seasonal And Pandemic Influenza

Photo Credit CDC PHIL 

# 8379

 

Despite decades of research, a surprising number of seemingly basic questions about the influenza virus, and the host’s immune response to infection, remain less than fully answered.  Questions like:

• How is the virus most commonly spread? (Aerosolized virus particles, Large Droplets, Fomites . . . )
• How long are we infectious?
• How effective are NPIs like masks, eye-protection, hand-washing, social distancing?
• How common are asymptomatic infections?
• Can (and do) asymptomatic carriers spread the virus to others?

As you might imagine, public policy decisions - such as when and how long we close schools, what protective gear we should require for health care workers, and how soon those who have been infected should be allowed to return to work - all hinge on having good answers to the above questions.

 

In recent years, research (see PLoS One: Influenza Viral Shedding & Asymptomatic Infections, Influenza Transmission, PPEs & `Super Emitters’ & Study: The Role Of Aerosols In The Spread Of Influenza) has shed considerable light on these issues, but the knowledge gained is incremental, and not always in complete agreement.

 

Today we’ve a major study appearing in The Lancet Respiratory Medicine, that uses  UCL’s FluWatch Study to compile perhaps the most comprehensive multi-year (2006-2011) serological analysis of community influenza we’ve seen to date.

 

The abstract from Cohort Profile: The Flu Watch Study describes the methodology, which involved 5,484 participants from 2,205 households in England.

 

Baseline data were collected on demographic, medical, social and behavioural risk factors and pre-season blood samples taken for immunological assays. Households were contacted weekly to report respiratory symptoms throughout the influenza season and asked to collect nasal swabs during respiratory illnesses for testing for a panel of respiratory viruses using PCR. Post-season blood samples, questionnaires and medical records checks were done.

 

While asymptomatic or sub-clinical infection with the influenza virus is already known to occur with some frequency, this study finds the rate of asymptomatic infection to be higher than commonly suspected.  As many as 75% of those who show serological evidence of infection reported no significant influenza symptoms.

 

First the Abstract, and link to the open access report (which is well worth reading in its entirety), after which I’ll be back with more.

 

Comparative community burden and severity of seasonal and pandemic influenza: results of the Flu Watch cohort study

Dr Andrew C Hayward MD a , Ellen B Fragaszy MSc a c, Alison Bermingham PhD d, Lili Wang PhD f, Andrew Copas PhD a, W John Edmunds PhD c, Neil Ferguson DPhil h, Nilu Goonetilleke PhD f g, Gabrielle Harvey MPH a, Jana Kovar PhD a, Megan S C Lim PhD a i, Andrew McMichael PhD f, Elizabeth R C Millett MSc a c, Jonathan S Nguyen-Van-Tam DM j, Irwin Nazareth PhD b, Richard Pebody MBChB e, Faiza Tabassum PhD a, John M Watson FRCP e, Fatima B Wurie BSc a, Prof Anne M Johnson MD a †, Maria Zambon PhD d †, on behalf of the Flu Watch Group

Summary

Background

Assessment of the effect of influenza on populations, including risk of infection, illness if infected, illness severity, and consultation rates, is essential to inform future control and prevention. We aimed to compare the community burden and severity of seasonal and pandemic influenza across different age groups and study years and gain insight into the extent to which traditional surveillance underestimates this burden.

Methods

Using preseason and postseason serology, weekly illness reporting, and RT-PCR identification of influenza from nasal swabs, we tracked the course of seasonal and pandemic influenza over five successive cohorts (England 2006—11; 5448 person-seasons' follow-up). We compared burden and severity of seasonal and pandemic strains. We weighted analyses to the age and regional structure of England to give nationally representative estimates. We compared symptom profiles over the first week of illness for different strains of PCR-confirmed influenza and non-influenza viruses using ordinal logistic regression with symptom severity grade as the outcome variable.

Findings

Based on four-fold titre rises in strain-specific serology, on average influenza infected 18% (95% CI 16—22) of unvaccinated people each winter. Of those infected there were 69 respiratory illnesses per 100 person-influenza-seasons compared with 44 per 100 in those not infected with influenza. The age-adjusted attributable rate of illness if infected was 23 illnesses per 100 person-seasons (13—34), suggesting most influenza infections are asymptomatic. 25% (18—35) of all people with serologically confirmed infections had PCR-confirmed disease. 17% (10—26) of people with PCR-confirmed influenza had medically attended illness. These figures did not differ significantly when comparing pandemic with seasonal influenza. Of PCR-confirmed cases, people infected with the 2009 pandemic strain had markedly less severe symptoms than those infected with seasonal H3N2.

Interpretation

Seasonal influenza and the 2009 pandemic strain were characterised by similar high rates of mainly asymptomatic infection with most symptomatic cases self-managing without medical consultation. In the community the 2009 pandemic strain caused milder symptoms than seasonal H3N2.

Funding

Medical Research Council and the Wellcome Trust.

The bottom line is that during this five-year study period, just under 20% of the (unvaccinated) study cohort contracted the flu each year, but of those, roughly three-quarters did so without displaying classic influenza symptoms. 

 

There are limitations to this study, of course, including low participation rates, no data gathered from patients < 5 years of age, self-reporting of symptoms, and difficulty in obtaining a fully representative sample.

 

Still, the authors report that `Participants were generally highly diligent at completing weekly illness reports and submitting nasal swabs during illness (>85% completion)’.

 

In a related commentary (see Community studies of influenza: new knowledge, new questions),  Dr Peter William Horby  writes:

 

"In view of the undoubtedly high rates of subclinical influenza infection, an important unanswered question is the extent to which mild and asymptomatic influenza infections contribute to transmission…A large number of well individuals mixing widely in the community might, even if only mildly infectious, make a substantial contribution to onward transmission."

 

The question of asymptomatic transmission is an important one, and may well explain the lack of success in interdicting flu carriers at airports and border checkpoints during the 2009 pandemic (see Pathogens At the Gate).  While many nations are quick to set up thermal scanners at entry points, the evidence that they can forestall a virus from entering a country is seriously lacking (see Branswell: Limitations Of Airport Disease Screening).

 

Similarly, telling people who are sick to stay home during an epidemic (while excellent advice), isn’t a panacea to prevent community transmission if 75% of those infected are unaware of the fact they are infected. 

 

The good news in all of this is that 75% of people who get the flu don’t get sick enough to notice it.

 

The bad news is, influenza stealthily infects far more people each year than surveillance would suggest.  And that means that should a highly contagious (and pathogenic) novel virus emerge, controlling its spread may be more challenging than previously envisioned.

 

For more on the plans to mitigate the spread of influenza during a pandemic, you may wish to revisit:

 

Pandemic Preparedness: Taking Our Cue From The Experts

NPM13: Pandemic Planning Assumptions

CDC: Updated H7N9 Guidance Docs

Korea: Asymptomatic H5N1 Seropositive Cullers In Previous Outbreaks

Photo Credit – CDC PHIL

 

# 8266

 

There’s a bit of controversy brewing today as it has emerged that 10 people in Korea – involved in the culling of poultry during H5N1 outbreaks in 2003 and 2006 -  developed antibodies to the bird flu virus . . . yet were never admitted as having been `infected’ by the Korean government.

 

First the report (h/t Gert van der Hoek on FluTrackers) from the Korean Broadcasting System (KBS).

 

Asymptomatic Human Carriers of AI Confirmed in S. Korea

Write : 2014-02-04 09:09:57 Update : 2014-02-04 19:00:37

The government has confirmed it discovered cases of humans infected with avian influenza during previous outbreaks in South Korea.

The Korea Centers for Disease Control and Prevention confirmed ten people who culled birds during outbreaks in 2003 and 2006 had antibodies for the H5N1 strain of avian influenza.

The discovery of antibodies in those people means they were infected with the virus at some point, but the disease control agency said they were “asymptomatic carriers” who displayed no symptoms.

The government confirmed infections of bird flu in dead migratory birds throughout the country last month.

 

Another report from the Korea Times today, brings us badly timed government assurances that the new H5N8 virus is `unlikely to infect humans’,  as it also carries details of this story.

 

'Bird flu unlikely to infect people'

2014-02-04 16:55

By Nam Hyun-woo

(Excerpt)

 It said that there have been no reported cases of human infection from other avian influenza subtypes in Korea, such as H5N1 and H7N9, which have killed people in overseas outbreaks.

However, concern is growing over the CDC’s methods of determining human infection.

The national disease control center follows the World Health Organization’s standard when it assesses a human infection case. The WHO determines a person has been infected with avian influenza only when they show symptoms of acute respiratory disease. People who are asymptomatic, even though the virus has infiltrated their body, are not deemed cases of human infection.

When the H5N1 strain swept the country in 2003-2004 and 2006-2007, the CDC found antibodies in the blood serum of 10 people who had slaughtered chickens.

The fact that they had antibodies shows that their immune system was countering a viral infection.

“Since those 10 people showed no symptoms, they were not counted as human infection cases,” an official at the CDC said.

There is admittedly a range of opinions when it comes to defining whether someone is – or has been – infected with by a virus, but one can’t help but feel that the `higher standard’ employed here was more for political expedience than for scientific merit. 

 

When it comes to a virus like H5N1, there is considerable advantage in being able to say that `no human infections’   have been detected.

 

At issue is whether serological testing - testing for post-exposure antibodies - is a valid indication of viral infection.  And given the emphasis we’ve seen on the need for serological testing to quantify the impact of just about every viral outbreak, you’d have to believe the answer is in the affirmative.

There are, of course, limits to serological tests, just as there are to PCR and viral cultures.  No test is perfect.  

 

Disagreements exist over what constitutes a `positive’  serological test (usually defined as a 4-fold increase in post-exposure antibody titer levels), and there are always concerns over potential cross-reactive antibodies and false positives.

 

But serological studies are generally regarded as the best way to determine the incidence of infection in a population, as you don’t have to depend upon a `perfect catch’ of a biological sample while the patient is actively shedding virus particles. 

 

Not stated in today’s articles are the antibody titer levels detected in these 10 cases, so there could be some wiggle room there. 

 

But it is also likely that these cullers were placed on Tamiflu while they were working with infected birds, which would probably have affected the antibody titers they developed, as well as suppressing any outward symptoms.  

In the past we’ve often seen seroprevalence studies used to quantify avian flu infections in humans, including:

 

• Two years ago, in H5N1 Seroprevalence Among Jiangsu Province Poultry Workers, we saw a study that found across 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 2011, a study (see Subclinical H5 & H9 Infections In Humans) tested 605 residents in and around Beijing China for antibodies to H5 and H9 avian flu viruses.  Of these, just  5 (less than 1%) had antibodies to H9 avian influenza, and only 1 was positive for antibodies to H5.
• In May of 2009 (see Cambodian Study Finds Rare Asymptomatic H5N1 Infections) we saw a study published in the Journal of Infectious Diseases 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.
• 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.

 

So it is hard to argue that the detection of antibodies – even in asymptomatic cases – wasn’t worthy of mention, even if the official determination was they were not `infected’.

 

While hardly a game changer, and not terribly surprising given other H5N1 studies we’ve seen -  this is scientific data and it should have been disclosed in a timely fashion - not held back for a decade.

 

If for no other reason than now – as Korea finds itself in the midst of another avian flu crisis – everyone will be wondering what other `hidden asterisks’  are attached to government assurances.

As I’m not a virologist or an epidemiologist, I’ll leave it to those more qualified to argue the relative merits of using serological test results, or the exclusion of asymptomatic cases, in case definitions.   

 

Hopefully we’ll get far more expert reaction from Dr. Ian Mackay on all of this later today.

 

UPDATE:  Ian has now posted his thoughts at:

 

Why have a case definition that seems designed to miss transmission events?