Tuesday, June 28, 2016

Saudi MOH: 2 More Primary MERS Cases


While reports from our two recent outbreaks (Riyadh & Najran) take a break, we've two new primary (community acquired) cases, one with camel contact and the other without a known risk exposure.

Additionally, one death of a previously reported case from Hail was reported.

Is Something New Killing Poultry In Egypt?


Since it first arrived in the Middle East just over a decade ago, avian H5N1 has devastated Egypt's poultry sector, and has produced hundreds of human infections and more than 115 deaths.

The chronic use of older, often ineffectual vaccines (see 2012's A Paltry Poultry Vaccine) helped to spread  H5N1, and likely contributed to the Emergence Of A Novel Cluster of H5N1 Clade in 2014.  

In addition to H5N1, LPAI H9N2 is also endemic in Egypt's poultry, and while Egypt hasn't reported it to the OIE - earlier this month in PLoS One: Serological Evidence Of Human Infection with Avian H7 in Egyptian Poultry Growers - we saw circumstantial evidence of avian H7 in Egypt's poultry.

Testing, surveillance, and reporting out of Egypt has been seriously lacking in recent years, and so it is very difficult to know exactly what the situation is there. 

But earlier this month, in HPAI H5 Worries From Egypt's Poultry Sector we saw reports of greatly increased poultry deaths, and concerns that HPAI H5N8 might have arrived in Egypt as well.

After launching an investigation, on June 9th Egypt's Ministry of Agriculture announced Initial Tests were Negative For H5N8, but the cause of the excess mortality remained unknown. 

Reports of unusual poultry losses have continued, and in the past few days Egyptian media have begun reporting on a new syndrome - الالتهاب الارتعاشى -  which translates to Inflammation tremens, that is reportedly spreading rapidly.
The Egyptian Ministry of Agriculture's website - which is only rarely updated - has been unreachable for me the past few days, so I've not found any official statement on this syndrome.

We do have one of the many syntax-challenged Arabic media reports on this crisis posted this morning by Sharon Sanders of Flutrackers called Three crises besieging the poultry industry.

While it briefly describes the new `epidemic' it spends most of its time quoting an industry representative's criticisms of the  MOA for a long list of shortcomings, including failing to provide effective vaccines.

A few excerpts follow:

The poultry sector faces severe crises since the beginning chapters since the emergence of the bird flu virus in 2006 caused the retreat despite industry achieved before it jumps the productivity, where production exceeds $ 2 million birds a day.


This year a new epidemic is severe tremens a disease do not have veterinary services special vaccines vaccines to meet it, leading to massive deaths of poultry farms.
Dr. Abdulaziz Al Sayed, head of the massacres and poultry Cairo Chamber of Commerce Division, that the current crisis is the most powerful crises experienced by the sector since the avian flu crisis in virus emerges in 2006, pointing out that the fundamental problem facing the sector is not the emergence of the virus and to reverse and return production to normal visits but other lies in the working methods in the sector, whether producers or the Ministry of Agriculture or government decisions, which resulted in many errors that made this sector groaning

He referred to the Ministry of Agriculture failed to work serums strong and vaccines that can cope with bird flu even though the settlers of the virus in Egypt for more than 9 years, they resorted to import vaccines and vaccines from abroad, which it increased both the emergence of inflammation tremens is a new virus does not have the body serum is able to confront what led to the deaths of large numbers of more than 40% of production
(Continue . . . )

Given the vague nature of these reports, and the lack of comment by the MOA, it is impossible to know exactly what is going on with Egypt's poultry sector, beyond the fact they are dealing with a crisis.

But with Egypt's history of avian flu expansion and evolution, hopefully we'll get some clarification on all of this sooner rather than later.

DRC's Plan To Vaccinate 11.6 Million Against Yellow Fever


Just over 10 days ago, in WHO: Lower Doses Of Yellow Fever Vaccine Could Be Used In Emergencies - in view of Africa's ongoing Yellow Fever outbreak and a shortfall in global vaccine supplies - we saw their SAGE (Strategic Advisory Group of Experts) on immunization approve the use of `fractional dose' vaccination in an emergency.

While fractional dosing greatly extends the supply of available vaccine, the downside is recipients would be unlikely to gain lifetime immunity (more likely 12 months or so), and would not receive a standard yellow fever vaccination certificate. 

The decision announced on June 17th was described as an emergency fall-back plan, with the WHO stating the situation didn't currently call for its implementation, but if the situation in Africa worsened substantially . . . .

Fast forward a little over a week and the Health Minister of the DRC has announced plans to vaccinate the entire population (over the age of 9 mos) of the capital -  Kinshasa -  and target populations in Kwango, Lualaba and Kasai provinces. 

With reportedly only 1.6 million doses of vaccine available in the DRC - even if diluted to 1/5th strength - it isn't clear how they will obtain enough vaccine to provide the estimated 11.6 million doses required.

Six days ago the WHO announced the Launch of emergency vaccination campaigns on the DR Congo and Angola border (see below), but this new plan would seem to far exceed it in the DRC.

    Brazzaville, 22 June 2016 – As the yellow fever outbreak in Angola and Democratic Republic of the Congo continues, the World Health Organization will launch emergency pre-emptive vaccination campaigns on the DR Congo, Angola border and the city of Kinshasa in the DR Congo to halt the epidemic and prevent the risk of further international spread.
    The initial phase of the campaign which begins in July will focus on districts where there is high movement of people and intense trade activities, particularly the northern border districts of Angola and targeted border districts in neighbouring countries. Specifically, within a 75-100km belt spanning the border between Angola and DR Congo and targeted health zones/communes at risk in Kinshasa city in the DR Congo. This will create an immune buffer to prevent further international spread.

    So far, I haven't seen any official comment from the WHO on the DRC's more aggressive plan.  The most complete coverage of the DRC's decision comes from VOA NEWS.

    Congo Launches Vaccination Campaign Against Yellow Fever

    VOA News

    June 27, 2016 8:15 PM

    The Democratic Republic of Congo says it will begin a campaign next month to vaccinate 11.6 million people against yellow fever after an epidemic was declared in the capital.

    Health Minister Felix Kabange said the campaign will begin July 20 and will aim to vaccinate everyone in the capital of Kinshasa except children under nine months, and will also target populations in the provinces of Kwango, Lualaba and Kasai.

    Last week, Congo's government announced an epidemic in Kinshasa and two other provinces after reporting 67 confirmed cases of yellow fever and more than 1,000 other suspected cases. An outbreak in neighboring Angola has led to the deaths of about 345 people.

    Kabange did not say how health authorities would acquire enough vaccination doses for the campaign. The vaccine is in short supply around the world, and takes about a year to make.

    The World Health Organization recommended this month that the vaccine be diluted up to a fifth of the standard dose to deal with the current emergency.

    The WHO says the lower dosage will protect people for at least a year, but will likely not give lifelong immunity.

    (Continue . . . )

    Monday, June 27, 2016

    Nature Sci Rpts: Continued Evolution Of The 2009 H1N1 Virus

    Credit NIAID


    In August of 2010, roughly 16 months after the new H1N1 virus first emerged, the WHO finally declared the end of the 2009 Pandemic.

    For most people the switch over to seasonal status signaled the pH1N1 threat was over.

    But of course, seasonal influenza kills hundreds of thousands of people each year, and as we've seen, some seasons are much worse than others.

    In the United States, the 2011-2012 and the 2015-2016 flu seasons were unusually mild (see chart above), while the years in-between were moderately severe.

    The severity of flu can also be regional, as we've seen severe flu outbreaks reported in India, Eastern Europe, and the Middle East at the same time there was relatively little flu in North America (see WHO: Update On Ukraine's Flu Season).

    While some of the reasons behind this variance in flu severity remain murky, two factors - the waxing and waning levels of community immunity and antigenic (and other) changes in the virus - appear to be major factors.

    Although the hope is always that the longer a virus circulates in a host population, the less severe it will become, the other side of the coin is the longer it circulates, the more evolutionary changes it may acquire.

    And that could not only make it more transmissible, it could make it more virulent as well.

    The most recent ECDC Influenza Virus Characterization report describes pH1N1's evolution:
    Since 2009, the HA genes have evolved, and nine clades have been designated. For well over a year, viruses in clade 6, represented by A/St Petersburg/27/2011 and carrying amino acid substitutions of D97N, S185T and S203T in HA1 and E47K and S124N in HA2 compared with A/California/7/2009, have predominated worldwide with a number of subclades emerging.

    In other words, the 2009 H1N1 viruses of today are markedly different from those that emerged in the spring of 2009, and they continue to evolve and diversify.

    Some mutations in pH1N1 - including the D225 Variant linked to more severe deep lung infection and the H275Y mutation conferring antiviral resistance -  are worrisome, but are seen in fewer than 2% of samples and are not yet viewed as major public health concerns. 

    But today we've a study, published in Nature's Science Reports, that identifies 6 genetic changes (PA-L581M, NP-V100I, NP-I373T, HA-S202T, NA-N248D and NS1-I123V) that appeared shortly after the virus jumped from pigs to humans, and that are still seen in 99% of the pH1N1 viruses circulating today. 

    These changes appear to to be the result of host adaptation, are believed to have made the pH1N1 a more `humanized' virus, conferring greater transmissibility and improved viral fitness. 

    This study has significance beyond just pH1N1, as it suggests the longer a poorly adapted virus influenza circulates in humans (think: H7N9, H5N1, H1N1v, H3N2v, etc.), the better its chances are of adapting to human hosts.  

    It's a long, fascinating article, and the abstract only scratches the surface, so you'll want to follow the link to read it in its entirety.

    I'll have a bit more when you return. 

    Evolution of 2009 H1N1 influenza viruses during the pandemic correlates with increased viral pathogenicity and transmissibility in the ferret model.


    There is increasing evidence that 2009 pandemic H1N1 influenza viruses have evolved after pandemic onset giving rise to severe epidemics in subsequent waves.However, it still remains unclear which viral determinants might have contributed to disease severity after pandemic initiation.

    Here, we show that distinct mutations in the 2009 pandemic H1N1 virus genome have occurred with increased frequency after pandemic declaration. Among those, a mutation in the viral hemagglutinin was identified that increases 2009 pandemic H1N1 virus binding to human-like α2,6-linked sialic acids. 

    Moreover, these mutations conferred increased viral replication in the respiratory tract and elevated respiratory droplet transmission between ferrets. 

    Thus, our data show that 2009 H1N1 influenza viruses have evolved after pandemic onset giving rise to novel virus variants that enhance viral replicative fitness and respiratory droplet transmission in a mammalian animal model. 

    These findings might help to improve surveillance efforts to assess the pandemic risk by emerging influenza viruses.
    (BIG SNIP)

    In summary, our findings here suggest that increased vigilance in viral surveillance is required even after pandemic onset since IAV seem to harbour the potential to further evolve causing severe subsequent epidemics in the human population.

    In 1957, after almost 40 years where H1N1 had dominated the global flu world, a new H2N2 virus appeared, and sparked a fresh pandemic.

    The Asian flu was less severe than 1918, but more severe than 1968 and 2009, and probably killed around 4 million people.

    As the chart below illustrates, intermittent severe outbreaks of that virus continued beyond the pandemic period, with H2N2 returning every few years with renewed vigor.

    We saw similar spikes in H1N1 in the decade following the 1918 pandemic, with peaks reported in 1923, 1926 and 1929 (see The Pandemic Influenza Enigma).

    While we are always on watch for a novel flu to appear, sparking the next pandemic, history has proven time and again that sometimes even an old flu can learn new tricks.

    So we watch for changes in both of our seasonal influenza A viruses, always  mindful that either of them could produce a particularly nasty flu season down the road.  

    UK PHE Stands By The Nasal Spray Flu Vaccine


    It's a case of `PHE said - CDC said', but there's a sharp division between the two public health agencies over the effectiveness of the LAIV (live attenuated influenza vaccine) called FluMist Quadrivalent in the US market and Fluenz Tetra in the UK and EU market.

    Both products are manufactured by AstraZeneca - Medimmune, and while sold under different banners, are pharmaceutically identical. 

    Last week, in CDC Statement On ACIP Recommendation Against Use Of Inhaled (LAIV) Flu Vaccine, we looked at the surprising (and as yet, unexplained) drop in VE (vaccine effectiveness) of the inhaled flu vaccine reported by the CDC over the past three flu seasons.

    After years of posting superior VE numbers, the first signs of trouble appeared in the fall of 2014 when the CDC announced they could find no measurable effectiveness against the H1N1 strain among children who received the 2013-2014 vaccine.

    The LAIV posted another poor showing (against both H1N1 and a `drifted' H3N2) the following year (see CIDRAP ACIP drops preference for nasal-spray flu vaccine in kids).

    And just last week, after reviewing yet another disappointing set of VE numbers from last year's flu season, ACIP voted against recommending the nasal spray LAIV vaccine for the upcoming flu season.

    Citing their own studies, and a study from Finland, the UK's PHE finds the performance of the LAIV (57%) in children to be lower than commonly cited in previous years, but still acceptable and on par with the flu jab in adults. 

    Why there would be such a stark difference between the US and UK VE studies is a mystery.   In any event, the UK continues to support the use of the LAIV vaccine for the upcoming flu season.  

    This from the PHE.

    Child flu vaccine plays important role in annual flu programme

    Provisional figures show that the nasal spray flu vaccine has been effective in the UK.

    Public Health England (PHE), the Department of Health and NHS England remain confident that the children’s nasal spray flu vaccine plays an important role in protecting children, their families and others in the community from flu during the winter.

    Provisional figures released by PHE show that the childhood nasal spray flu vaccine has been effective in the UK, both in protecting the children themselves and their communities from flu. Reports from the US have suggested a possible lower vaccine effectiveness, unlike the findings in the UK.

    The National Institute for Health and Welfare in Finland has confirmed that they saw similar effectiveness levels to the UK in 2015 to 2016 (46% against laboratory confirmed disease), and have confirmed the nasal spray flu vaccine will continue to be used in Finland for the forthcoming winter.

    From October 2016, the vaccine will be extended to healthy children in school year 3 in England. Once again, children aged 2, 3 and 4, and in school years 1 and 2 will also be eligible to receive the free vaccine which is quick, effective and painless.

    Dr Richard Pebody, head of flu surveillance for PHE said:

    We estimate that overall, the vaccine was 57.6% (95% confidence interval: 25.1, 76) effective in preventing influenza infection amongst children in 2015 to 2016. These findings are encouraging and in line with what we also typically see for the adult flu vaccine.
    Prior to offering vaccination to all our youngest primary school aged children this season, school age pilots took place in a number of areas across England in 2014 to 2015. In areas where flu vaccine was piloted amongst primary school age children, there was a 94% reduction in GP influenza like illness consultation rates, 74% reduction in A&E respiratory attendances and 93% reduction in hospital admissions due to confirmed influenza in primary school children. In the same pilot areas, GP ‘influenza like illness’ consultation rates for adults were 59% lower compared to non-pilot areas.

    Flu vaccine is the best protection we have against an unpredictable virus which can cause severe illness and deaths each year not only amongst children but also amongst at-risk groups, including older people, pregnant women and those with an underlying health condition.
    Based on intelligence to date, there is no reason to change current recommendations regarding use of the children’s nasal spray vaccine in the UK. We’re delighted that the UK leads the way in offering this vaccine to children and we remain confident that the vaccines used in the Annual Flu Vaccine programme are the most effective that are currently available in protecting both those vaccinated and in reducing transmission of the flu virus in our communities. We will continue to keep the vaccines used in our programmes under review and to take advice from our independent expert scientific committee, the Joint Committee on Vaccination and Immunisations (JCVI).
    PHE will publish a complete report in late summer 2016.
    PHE recently confirmed the use of the children’s nasal spray for the 2016 to 2017 flu vaccination programme through its annual flu plan and letter.

    ECDC Policy Briefing On Zika Virus

    Credit ECDC


    Although we've seen some signs suggesting Zika outbreaks may be less severe in communities without a prior history of Dengue transmission (see Nature Immunology: Previous Dengue Infection May Make Zika Infection Worse), we really don't know what impact this Asian Zika strain will have on an immunologically naive population - or for that matter - the number of people in Europe with previous Dengue exposure.

    It's a big unknown, and while North America and Europe seem highly unlikely to see widespread outbreaks, there are too many ways this could go badly to ignore the threat. 

    So for the past 6 months the ECDC has been rolling out a series of guidance documents, Rapid Risk Assessments, and (today) a policy briefing on Zika's threat to the EU.

    Preparing for Zika in the EU – Policy briefing

    27 Jun 2016

    ​To assist policymakers in preparing for possible local transmission of Zika in the EU, ECDC has produced a policy briefing which highlights preparedness measures to minimise the risk of Zika virus spreading in continental Europe. This is primarily to protect pregnant women and women who wish to become pregnant, considering the evidence of the association between Zika virus and congenital malformations of the brain of the developing foetus.

    Locally acquired cases of Zika virus infection are possible in the EU this summer in countries which have a large Aedes albopictus mosquito population (a mosquito capable of transmitting Zika), and where the ecological and climatic factors favour transmission. In the Autonomous Region of Madeira (Portugal), there is a higher probability of locally acquired cases of Zika than in continental Europe as the main mosquito capable of transmitting Zika, Aedes aegypti, is present there.

    Imported cases of Zika virus are already being seen in Europe as well as sexual transmission of Zika through travellers returning from affected areas, and this can be expected to continue given the high number of people travelling between the most affected regions and Europe.

    Failure to adequately prepare for Zika in the EU could lead to the disease spreading more widely, resulting in greater costs for mosquito control and care for affected people, and greater concern among the general public. The briefing suggests policymakers focus on operational plans for response measures, including the capability to detect and diagnose cases early and perform surveillance, and the provision of adequate resources to sustain enhanced mosquito control.