Friday, June 24, 2016

Front. Microbiol.: A Novel H1N2 Reassorted Influenza Virus In Chinese Pigs


China, which is (by far) the world's largest producer of pork (see chart below), raises as many pigs as the next 10 biggest pork producing countries combined.

And while swine around the world carry and spread a variety of H1, H2, and H3 Swine Influenza Viruses (SIVs), a 2013 survey of the Epidemic Status of Swine Influenza Virus in China also documented the presence of avian H3N8, H4N8, H5N1, H6N6, and H9N2 in Chinese pigs. 

Swine possess both avian-like (SAα2,3Gal) and human-like(SAα2,6Gal) receptor cells in their respiratory tract, making them susceptible to a wide variety of avian, human, and swine influenza viruses.

This allows them to act as a `mixing vessels', which can lead to the creation of new hybrid flu viruses.

As the diversity of the pool of flu viruses circulating in pigs increases, the odds of generating new biologically fit novel viruses increases. Over time, reassortants of reassorted viruses are generated, and we end up with viruses with multiple parental contributions.

Over the past several years we've seen both swine variant viruses (like H1N1v, H1N2v, & H3N2v) and novel swine/human flu variants emerge around the world.

A few recent blogs include:

Sci Rpts: Transmission & Pathogenicity Of Novel Swine Flu Reassortant Viruses
FluView: Novel H1N2v Flu Case Reported In Minnesota
WHO: H1N1v Cases In China
 PNAS: The Pandemic Potential Of Eurasian Avian-like H1N1 (EAH1N1) Swine Influenza,

Since the influenza subtypes that commonly circulate in swine (H1, H2 & H3) are also the same that have caused all of the human pandemics going back 130 years (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?), they are generally regarded as having less far to `jump’ to humans than many avian viruses.

Which is precisely how the H1N1 pandemic virus emerged in 2009, after kicking around (and reassorting in) swine herds for a decade or longer.

So we watch with interest reports - like the one below - of novel swine flu viruses emerging anywhere in the world. 

A Novel H1N2 Influenza Virus Related to the Classical and Human Influenza Viruses from Pigs in Southern China

Yafen Song1, Xiaowei Wu1, Nianchen Wang1, Guowen Ouyang1, Nannan Qu1, Jin Cui1, Yan Qi2, Ming Liao1* and Peirong Jiao1*
  1. College of Veterinary Medicine, South China Agricultural University, China
  2. China Animal Husbandry Group, China

Southern China has long been considered to be an epicenter of pandemic influenza viruses. The special environment, breeding mode, and lifestyle in southern China provides more chances for wild aquatic birds, domestic poultry, pigs and humans to be in contact. This creates the opportunity for interspecies transmission and generation of new influenza viruses. 
In this study, we reported a novel reassortant H1N2 influenza virus from pigs in southern China. According to the phylogenetic trees and homology of the nucleotide sequence, the virus was confirmed to be a novel triple-reassortant H1N2 virus containing genes from classical swine (PB2, PB1, HA, NP, and NS genes), triple-reassortant swine (PA and M genes) and recent human (NA gene) lineages.

It indicated that the novel reassortment virus among human and swine influenza viruses occurred in pigs in southern China.

The isolation of the novel reassortant H1N2 influenza viruses provides further evidence that pigs are ‘‘mixing vessels”, and swine influenza virus surveillance in southern China will provide important information about genetic evaluation and antigenic variation of swine influenza virus to formulate the prevention and control measures for the viruses.

The full (provisional) PDF of the report is available here.

Saudi MOH Announces 1 New Asymptomatic MERS Case In Riyadh



After three days with no new reports from Riyadh's extended nosocomial MERS outbreak, the MOH has announced a new asymptomatic hospital acquired case.

Between inconsistencies in the daily reports, delays in case announcements, and the recent umbrage taken by the Saudi's over the media coverage of this outbreak (see Crof's excellent WHO EMRO: Clarification on a MERS-CoV case in Saudi Arabia), it's difficult to know whether this outbreak is really on the wane.

But as it stands now, over the past 10 days Riyadh has reported more than 2 dozen cases.


DEFRA Outbreak Assessment: LPAI H7N9 In Netherlands

Credit DEFRA


The UK's DEFRA (Department for Environment, Food & Rural Affairs), which continues to be our best source of follow up and analysis of European bird flu outbreaks, has published an assessment of the Netherlands' LPAI H7N9 outbreak that I wrote about earlier this month.

As strongly suspected at the time, this LPAI H7N9 is of European origin, and is not related to the highly dangerous H7N9 virus which has been circulating in China since 2013. 

Unlike 2015, which saw several European outbreaks where LPAI viruses mutated into highly pathogenic (HPAI) strains, this outbreak remained LPAI. 

While European H7 viruses have on rare occasions produced sporadic ( and generally mild) human infections, Public Health England has determined the risk to the general public from this outbreak to be very low.

Preliminary Outbreak Assessment

Low Pathogenicity Avian Influenza, H7N9 in Netherlands

Ref: VITT/1200 LPAI H7N9 Netherlands

Disease Report

Netherlands has reported an outbreak of avian influenza in domestic laying hens in Friesland region. Over 48,000 birds were present on the premises in two production systems with outside access of 16,000 free range birds and 32,000 organic birds. The virus was reported as H7N9 low pathogenicity (OIE, 2016; see map) with only very mild clinical signs observed of slight egg drop and dullness. Disease control measures have been put in place, and the birds are being culled. There are no other premises in the 1km zone. Initial information suggests this is a European strain.

Situation Assessment

The last time this virus was detected in the EU was in 2009 in the Czech Republic.Domestic breeding geese were tested as part of routine surveillance activities. No clinical signs were observed. A case occurred in domestic ducks in France also in 2009. It is highly possible it has been circulating in wild birds in the intervening years.

As with this latest outbreak in the Netherlands was in laying hens, it is important that mild clinical signs, such as egg drop, are reported quickly, so testing can take place. This type of production system provides a suitable environment for viral circulation to take place and possible mutations to occur which lead to highly pathogenic viruses. Rapid, reactive control measures reduce the risk of these viruses spreading widely.

The strain is not the same as the Asian H7N9 LPAI strain circulating in poultry in China. It is a distinct classical European lineage virus consistent with the large reservoir of related viruses of multiple subtypes in European wild birds (Promed, 2016). The distinct lineage of Asian origin virus has been responsible for nearly 800 human cases and over 300 deaths since February 2013 (FAO, 2016). That particular strain is a result of multiple re-assortments of H9N2 and H7N3 viruses from domestic poultry, and H7N9 wild bird viruses. These re-assortment events take place in domestic poultry, possibly in live bird markets as well as poultry farms and there is continual evolution of these viruses over time, which is why vigilance and surveillance is important. 

However, in the three years since the virus was first reported in China, the Chinese authorities have carried out a high level of testing and surveillance in poultry as well as wild and captive birds and the virus has remained on the whole restricted to poultry in China. Very occasionally human cases have occurred in other countries, but these have all been associated with people who have travelled in China. There appears to be no wild bird reservoir for this strain of H7N9 virus which is well adapted to gallinaceous poultry and therefor domestic waterfowl are more refractory to infection.

Public Health England has confirmed the risk to the general public is very low. According to the EU Trade notification system, there has been no recent trade in either live poultry or hatching eggs from the region to the UK.


Our risk level remains the same, low but heightened, as there are several strains of avian influenza viruses which have been reported in recent months across Europe.

We would like to remind all poultry keepers to maintain high standards of biosecurity, remain vigilant and report any suspect clinical signs promptly and in addition using the testing to exclude scheme for avian notifiable disease where appropriate for early safeguard.

Thursday, June 23, 2016

Nature Immunology: Previous Dengue Infection May Make Zika Infection Worse


It's an idea that has been bandied about for many months, and strongly hinted at in a study published last April (see Dengue & Zika: Does What Goes Around, Come Around?), but we've new evidence today suggesting that those who have experienced a previous Dengue infection may be at greater risk of seeing a severe Zika virus infection.

Since Dengue is widespread in South and Central America, this could explain why Zika has hit those regions so hard over the past year. 

The idea is fairly simple, and it has previously been reported in sequential dengue infections. It is called ADE or Antibody Dependent Enhancement.

There are 4 distinct, but closely related, serotypes of the Dengue virus, and the first infection of any serotype is usually mild. The patient recovers with lifetime immunity, but remains susceptible to the other three serotypes.

When infected a second time,the host’s immune system - which already has neutralizing antibodies against the first DENV infection - misidentifies the second DENV infection as the first strain.

Rather than creating new neutralizing antibodies to fight the infection, it deploys its existing cross reactive, but non-neutralizing (read: ineffective) antibodies to the field of battle.

Zika is in the same family (Flaviviridae) of viruses as Dengue, and is genetically pretty close to the Dengue branch. So much so that diagnostic tests can have difficulty differentiating between the two infections.

So it makes sense that the same kind of ADE might occur when a Zika infection follows a Dengue infection. 

But lots of things can make sense.  It doesn't necessarily make it true.

While the results are preliminary, a study published today in the journal Nature Immunology suggests that existing dengue antibodies can recognize, and bind to, the Zika virus.

This could fool the body's immune system into sending unarmed (aka non-neutralizing) antibodies into battle against the invading Zika virus, and allow it to multiply rapidly. 

The full study may be read at:

Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus
Wanwisa Dejnirattisai, Piyada Supasa, Wiyada Wongwiwat, Alexander Rouvinski, Giovanna Barba-Spaeth,Thaneeya Duangchinda,Anavaj Sakuntabhai,Van-Mai Cao-Lormeau,Prida Malasit,Felix A Rey ,Juthathip Mongkolsapaya& Gavin R Screaton

Nature Immunology
Published online

Using a panel of human monoclonal antibodies (mAbs) to DENV, we showed that most antibodies that reacted to DENV envelope protein also reacted to ZIKV. Antibodies to linear epitopes, including the immunodominant fusion-loop epitope, were able to bind ZIKV but were unable to neutralize the virus and instead promoted ADE. Our data indicate that immunity to DENV might drive greater ZIKV replication and have clear implications for disease pathogenesis and future vaccine programs for ZIKV and DENV.

 (Continue . . . )

For a less technical overview, Imperial College has published a press release on this study:

Dengue virus exposure may amplify Zika infection

Imperial College London

Previous exposure to the dengue virus may increase the potency of Zika infection, according to research from Imperial College London.

The early-stage laboratory findings, published in the journal Nature Immunology, suggests the recent explosive outbreak of Zika may have been driven in part by previous exposure to the dengue virus.

The study, which included scientists from Institut Pasteur in Paris and Mahidol University in Bangkok, suggests the Zika virus uses the body's own defences as a 'Trojan horse', allowing it to enter a human cell undetected. Once inside the cell, it replicates rapidly.

Professor Gavin Screaton, senior author of the research and Dean of the Faculty of Medicine at Imperial, said: "Although this work is at a very early stage, it suggests previous exposure to dengue virus may enhance Zika infection. This may be why the current outbreak has been so severe, and why it has been in areas where dengue is prevalent. We now need further studies to confirm these findings, and to progress towards a vaccine."

A second study by the same team, published in Nature, suggests an antibody that works against the dengue virus may also neutralise Zika - providing a potential target for a vaccine.

Dengue fever has risen dramatically over recent decades and the virus is thought to cause around 390 million infections each year - with 40 per cent of the world's population living in areas of risk.

The dengue virus is similar to the Zika virus - they belong to the same viral family, called the Flaviviridae, and both are transmitted by the Aedes mosquito.

(Continue . . . )

Saudi MOH Announces 1 Primary Case In Jeddah



We've had three days without any new cases announced from Riyadh's hospital cluster, but we do have the third case reported from  Jeddah this week.  

On Tuesday we saw a primary case and a household contact, while today we have another primary case.  The circumstances of exposure for these two primary cases hasn't been announced.

Additionally, we have one death reported from Najran, of a primary case announced last on Saturday.


CDC Statement On ACIP Recommendation Against Use Of Inhaled (LAIV) Flu Vaccine

Credit CDC


Until a surprise announcement in the fall of 2014, the reputation of the LAIV (Live Attenuated Influenza Vaccine) nasal spray vaccine - particularly for children - was that it was more effective than the inactivated influenza vaccine (IIV) given as a shot.

Studies had been so positive until that time, that just four months earlier ACIP (Advisory Committee for Immunization Practices) had voiced a rare preference for the nasal mist vaccine over the shot for children (see CIDRAP ACIP cites preference for nasal-spray flu vaccine for young). 

But in November of 2014 the CDC announced that during the 2013-2014 season there was no measurable effectiveness for LAIV against influenza A (H1N1) among children enrolled in their Vaccine Effectiveness (VE) study.

The preference for the LAIV in children was revoked by ACIP in late February of 2015 after another poor showing (against both H1N1 and a `drifted' H3N2) during the 2014-2015 season (see CIDRAP ACIP drops preference for nasal-spray flu vaccine in kids).

Yesterday, after reviewing the most recent VE studies that showed little or no effectiveness during the 2015-2016 flu season, ACIP voted against recommending the nasal spray LAIV vaccine for the upcoming flu season.

Why the sudden poor showing for LAIV, after years of successful use, is unknown.  

ACIP's recommendations must be reviewed by the Director of the CDC before they become policy, but it would be unusual to see an override.

This statement from the CDC:

ACIP votes down use of LAIV for 2016-2017 flu season

Media Statement

For Immediate Release: Wednesday, June 22, 2016
Contact: Media Relations,
(404) 639-3286

CDC’s Advisory Committee on Immunization Practices (ACIP) today voted that live attenuated influenza vaccine (LAIV), also known as the “nasal spray” flu vaccine, should not be used during the 2016-2017 flu season. ACIP continues to recommend annual flu vaccination, with either the inactivated influenza vaccine (IIV) or recombinant influenza vaccine (RIV), for everyone 6 months and older.

ACIP is a panel of immunization experts that advises the Centers for Disease Control and Prevention (CDC). This ACIP vote is based on data showing poor or relatively lower effectiveness of LAIV from 2013 through 2016.

In late May, preliminary data on the effectiveness of LAIV among children 2 years through 17 years during 2015-2016 season became available from the U.S. Influenza Vaccine Effectiveness Network. That data showed the estimate for LAIV VE among study participants in that age group against any flu virus was 3 percent (with a 95 percent Confidence Interval (CI) of -49 percent to 37 percent). This 3 percent estimate means no protective benefit could be measured. In comparison, IIV (flu shots) had a VE estimate of 63 percent (with a 95 percent CI of 52 percent to 72 percent) against any flu virus among children 2 years through 17 years. Other (non-CDC) studies support the conclusion that LAIV worked less well than IIV this season. The data from 2015-2016 follows two previous seasons (2013-2014 and 2014-2015) showing poor and/or lower than expected vaccine effectiveness (VE) for LAIV.

How well the flu vaccine works (or its ability to prevent flu illness) can range widely from season to season and can be affected by a number of factors, including characteristics of the person being vaccinated, the similarity between vaccine viruses and circulating viruses, and even which vaccine is used. LAIV contains live, weakened influenza viruses. Vaccines containing live viruses can cause a stronger immune response than vaccines with inactivated virus. LAIV VE data before and soon after licensure suggested it was either comparable to, or better than, IIV. The reason for the recent poor performance of LAIV is not known.

Vaccine manufacturers had projected that as many as 171 million to 176 million doses of flu vaccine, in all forms, would be available for the United States during the 2016-2017 season. The makers of LAIV had projected a supply of as many as 14 million doses of LAIV/nasal spray flu vaccine, or about 8 percent of the total projected supply. LAIV is sold as FluMist Quadrivalent and it is produced by MedImmune, a subsidiary of AstraZeneca. LAIV was initially licensed in 2003 as a trivalent (three-component) vaccine. LAIV is currently the only non-injection-based flu vaccine available on the market.

Today’s ACIP vote could have implications for vaccine providers who have already placed vaccine orders. The ACIP recommendation may particularly affect pediatricians and other vaccine providers for children since data from recent seasons suggests nasal spray flu vaccine accounts for about one-third of all flu vaccines given to children.  CDC will be working with manufacturers throughout the summer to ensure there is enough vaccine supply to meet the demand.

CDC conducts vaccine effectiveness (VE) studies each season to estimate flu vaccine effectiveness. Today’s ACIP vote highlights the importance of measuring and evaluating the effectiveness of public health interventions, which can have significant implications for public health policy. The change in the ACIP recommendation is an example of using new available data to ensure public health actions are most beneficial. Influenza is a serious disease that causes millions of illnesses, hundreds of thousands of hospitalizations, and thousands or tens of thousands of deaths each year. While the protection offered by flu vaccines can vary, the flu shot’s overall VE estimate of 49 percent suggests that millions of people were protected against flu last season.

Today’s ACIP recommendation must be reviewed and approved by CDC’s director before it becomes CDC policy. The final annual recommendations on the prevention and control of influenza with vaccines will be published in a CDC Morbidity and Mortality Weekly Report (MMWR), Recommendations and Reports in late summer or early fall.

CDC has recommended an annual influenza vaccination for everyone ages 6 months and older since February 24, 2010. CDC and ACIP briefly had a preferential recommendation for nasal spray vaccine for young children (during 2014-2015); however, during the 2015-2016 season, influenza vaccination was recommended without any preference for one vaccine type or formulation over another.