Anhui Province Reports Their 1st H5N6 Infection

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Our H5N6 tracking map has gotten a lot more crowded over the past few weeks, with a 6th Chinese Province (Anhui) now reporting a human infection - just one week after Hunan province announced their first case.  

 A week before that, it was Hubei province reporting their first case.

After only recording 4 human H5N6 cases during the first 20 months following its emergence in April of 2014, over the past 6 months China has reported 9 new cases.

Despite this increase in human infection reports, all of these cases appear to be isolated, and we've seen no evidence of clustering, or human-to-human transmission. 

This notification today from Hong Kong's CHP.

CHP notified of additional human case of avian influenza A(H5N6) in Anhui  

The Centre for Health Protection (CHP) of the Department of Health (DH) was notified of an additional human case of avian influenza A(H5N6) in Anhui by the National Health and Family Planning Commission today (May 3), and again urged the public to maintain strict personal, food and environmental hygiene both locally and during travel.
The case involves an 65-year-old woman who lives in Xuancheng, Anhui.  With history of poultry contact before onset, the patient developed symptoms on April 24 and was admitted to a local hospital on April 27. She is now in critical condition.
From 2014 to date, a total of 13 human cases of avian influenza A(H5N6) have been reported by the Mainland health authorities.
"All novel influenza A infections, including H5N6, are statutory notifiable infectious diseases in Hong Kong," a spokesman for the CHP said.
"We will remain vigilant and work closely with the World Health Organization and relevant health authorities to monitor the latest developments," the spokesman said.

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For more background on this emerging avian flu threat, you may wish to revisit these  blogs from last year:

H5N6: The Other HPAI H5 Threat

H5N6 Rising: Infecting Birds, Humans, & Even Cats

EID Journal: Influenza A(H5N6) Virus Reassortant, Southern China, 2014

Pediatrics: Maternal Flu Vaccination Extends Protection To Infants

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Today we've another, very large, multi-year study that finds substantial immunity to influenza is passed on to the infant - who cannot be immunized until 6 months of age - when the mother gets the flu vaccine during pregnancy.


From the University of Utah Health Sciences press release:

In a study published May 3, 2016, in Pediatrics online, University of Utah School of Medicine researchers reported that infants 6 months and younger whose mothers were vaccinated when pregnant had a 70 percent reduction in laboratory-confirmed flu cases and an 80 percent reduction in flu-related hospitalizations compared with babies whose moms weren't immunized. Health records showed that 97 percent of laboratory-confirmed flu cases occurred in infants whose mom's were not immunized against the disease while pregnant.

You may recall that five years ago, in Pssst! Immunity . . . Pass it On, we saw a study in the American Journal of Obstetrics and Gynecology, that found that maternal receipt of the flu vaccine was linked to more than a 45% reduction in infant hospitalizations with laboratory confirmed flu.


And similarly, in 2010, in Study: Protecting Two With One Shot  we saw a study in the Archives of Pediatric and Adolescent Medicine, that found that that babies born to mothers who received the flu vaccination experienced fewer infections and hospitalizations during their first six months than babies whose mothers did not.


Below you'll find a link and the abstract to today's study.  When you return, I'll have a bit more. 

Influenza in Infants Born to Women Vaccinated During Pregnancy

Julie H. Shakib, Kent Korgenski, Angela P. Presson, Xiaoming Sheng, Michael W. Varner, Andrew T. Pavia, Carrie L. Byington

Abstract

BACKGROUND: Infants  less than 6 months old with influenza are at risk for adverse outcomes. Our objective was to compare influenza outcomes in infants less than 6 months old born to women who did and did not report influenza vaccine during pregnancy.

METHODS: The study included all women who delivered from 12/2005 to 3/2014 at Intermountain facilities and their infants. Influenza outcomes included infant influenza-like illness (ILI), laboratory-confirmed influenza, and influenza hospitalizations.

RESULTS: The cohort included 245 386 women and 249 387 infants. Overall, 23 383 (10%) pregnant women reported influenza immunization. This number increased from 2.2% before the H1N1 pandemic to 21% postpandemic (P < .001). A total of 866 infants less than 6 months old had ≥1 ILI encounter: 32 (1.34/1000) infants born to women reporting immunization and 834 (3.70/1000) born to women who did not report immunization (relative risk [RR] 0.36; 95% confidence interval [CI], 0.26–0.52; P < .001). A total of 658 infants had laboratory-confirmed influenza: 20 (0.84/1000) born to women reporting immunization and 638 (2.83/1000) born to unimmunized women (RR 0.30; 95% CI, 0.19–0.46; P < .001). A total of 151 infants with laboratory-confirmed influenza were hospitalized: 3 (0.13/1000) born to women reporting immunization and 148 (0.66/1000) born to unimmunized women (RR 0.19; 95% CI, 0.06–0.60; P = .005).

CONCLUSIONS: Self-reported influenza immunization during pregnancy was low but increased after the H1N1 pandemic. Infants born to women reporting influenza immunization during pregnancy had risk reductions of 64% for ILI, 70% for laboratory-confirmed influenza, and 81% for influenza hospitalizations in their first 6 months. Maternal influenza immunization during pregnancy is a public health priority.

• Accepted March 3, 2016.

• Copyright © 2016 by the American Academy of Pediatrics

The list of maternal vaccination benefits goes on, both in and outside the womb.


Just over a month ago in Clinical Infectious Diseases: Flu Vaccine May Reduce Incidence of Stillbirth we saw a study that found  vaccinated mothers were 51 percent less likely to experience a stillbirth than unvaccinated mothers.

Last year in Pregnancy, Flu and The Next Pandemic we looked at the heightened flu risks for pregnant women, including a 2011 study - BMJ: Perinatal Outcomes After Maternal 2009/H1N1 Infection -  that found that pregnant women admitted to the hospital during the 2009 pandemic with H1N1 saw a 3 to 4 times higher rate of preterm birth, 4 to 5 times greater risk of stillbirth, and a 4 to 6 times higher rate of neonatal death.
 

Over the past decade we’ve also seen a handful of studies tentatively linking prenatal exposure to influenza (or an influenza-like-illness) with a variety of child and adolescent development disorders (see Of Pregnancy, Flu & Autism).

All of which explains why the CDC, the WHO, and other public health promote the seasonal flu vaccination of pregnant women.  Most years, the vaccine provides moderate protection against circulating flu strains, but in the event a pregnant woman becomes infected, studies also show the Benefits Of Early Use of Influenza Antivirals In Pregnancy.

  

OIE Notification: HPAI H7N7 In Italy

Credit OIE -Emilia-Romagna, Italy

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Except for France, Europe has seen remarkably few avian flu outbreaks in 2016, although last December we did see Italy: LPAI H5N2 On A Turkey Farm in the Emilia-Romagna administrative Region of Northern Italy.

Today, however, the OIE reports on an HPAI H7N7 outbreak - again in Emilia-Romagna - involving layer hens.

Human infection with H7N7, while rare (and generally mild), was documented as recently as 2013 (see ECDC Update & Assessment: Human Infection By Avian H7N7 In Italy)  and in a much larger outbreak more than a dozen years ago (see  Eurosurveillance Journal Human-to-human transmission of avian influenza A/H7N7, The Netherlands, 2003.


Despite these cases - with the exception of China's H7N9 virus - most avian H7 viruses are considered primarily a threat to the poultry industry.

Source of the outbreak(s) or origin of infection    

    Unknown or inconclusive

Epidemiological comments   

The positivity regards a commercial farm of layer hens (free-range/organic). Increased mortality rate was reported during the last two to three days. A protection zone of three kms and a surveillance zone of ten kms have been established around the farm, which is under restriction. Depopulation has been completed. 

Control measures
Measures applied    

    Disinfection / Disinfestation
    Traceability
    Stamping out
    Official disposal of carcasses, by-products and waste
    Surveillance within containment and/or protection zone
    Vaccination prohibited
    No treatment of affected animals

Egypt: FAO Reports Human LPAI H9 Infection

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Although not viewed as posing nearly the threat of H5N1, H9N2 infections in humans are worthy of our attention since they appear to be rare, and because the H9N2 virus has a habit of reassorting with other flu viruses.  

Its internal genes can be found in such novel flu viruses as H5N1, H5N6, and H7N9.  

On the positive side, H9N2 infection in humans has generally been mild, and no human-to-human transmission has been detected.

It's mild presentation, and the extremely limited amount of testing of mild flu infections globally, makes it difficult to know just how prevalent human infections really are - particularly in Asia and the Middle East - where it is pervasive in poultry. 

Last February, after an H9N2 case was reported from China,  the WHO wrote:

A total of 28 laboratory-confirmed cases of human infection with avian influenza A(H9N2) viruses, none fatal, have been detected globally. In most human cases, the associated disease symptoms have been mild and there has been no evidence of human-to-human transmission.  Influenza A(H9N2) viruses are enzootic in poultry populations in parts of Africa, Asia and the Middle East. The majority of viruses that have been sequenced belong to the A/quail/Hong Kong/G1/97 (G1), A/chicken/Beijing/1/94 (Y280/G9), or Eurasian clades.

The most complete list of H9N2 we have online can be found at FluTrackers Global Cumulative H9N2 Partial Case List 1998-2016. 


While details are very scant, today we have an FAO notification of a human infection with LPAI H9 (which is presumably, H9N2) in Egypt (see below).  

With 9 cases reported last year (4 in China, 3 in Egypt, 2 in Bangladesh), 2015 was a record year for H9N2 reports, although this jump may have more to do with Egypt & China ramping up their testing for novel flu viruses, than an actual increase in cases.


As with all influenza viruses, H9N2 is constantly changing, and we continue to see new variants emerge and take hold in different parts of the world.

• As far back as 2010 (see Study: The Continuing Evolution Of Avian H9N2) we looked at computer modeling (in silica) that warned the H9N2 virus has been slowly evolving towards becoming a `more humanized’ virus. 
• Two years ago, in PNAS: Evolution Of H9N2 And It’s Effect On The Genesis Of H7N9 we looked at research that showed a new, better adapted genotype  (G57) of the H9N2 virus had emerged in China  – one that evades the poultry vaccines currently in use – and that it has become widespread among vaccinated Chinese poultry since 2010.
• Last fall, in EID Journal: Replication Of Avian H9N2 In Pet Birds, Chickens, and Mammals, Bangladesh, we looked at research that found the Bangladeshi version is a novel reassortant that has acquired some mammalian adaptations along the way, finding the virus replicates well in human and swine tissues. 
• And only last month we looked at  A Canine H3N2 Virus With PA Gene From Avian H9N2 - Korea

Whether a standalone H9N2 virus ever poses a pandemic threat or not, it continues to aid and abet in the creation of new, often dangerous, bird flu viruses. That alone makes it worthy of our attention, although any substantial increase in human infection would be of concern as well.

Qatar MOH Statement On A New MERS Case

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Qatar announces their second MERS case of 2016 (and 15th to date) - although technically the first case of 2016 fell ill while living in Saudi Arabia and was diagnosed when he returned home for treatment.

Of Qatar's 15 reported cases, 1/3rd (n=5) appear to have been infected outside of the country.   

Today's case (h/t Tetano on FluTrackers), however, involves a 40 y.o. camel worker who has neither been out of the country, or in contact with a known MERS case in recent weeks. This from Qatar's MOPH :

MOPH announces 2nd (MERS-CoV) case in 2016

Publication Date: 02 May 2016

Category: Primary News

Ministry of Public Health (MOPH) has announced that a new Middle East Respiratory Syndrome Corona Virus (MERS-CoV) case has been confirmed for a 40-years old resident works as a camel worker in Qatar, marking the second MERS-CoV case to be confirmed in the country in 2016.

---

The case, who neither was in contact with a suspected case nor he has been abroad during the last two weeks, is free from chronic diseases that usually cause immunity suppression. He was admitted to Hamad General Hospital with general symptoms where the routine investigations tested positive for MERS-CoV despite he did not exhibit any respiratory related symptoms. The patient currently in stable condition and receives the necessary medical care in the isolation ward according to the national protocol of the infection prevention and control.

Once the case has been confirmed, the rapid response team of MOPH has carried out extensive search to list all potential contacts with the purpose to check for their possible consistence with the standard case definition of the suspected cases based on the WHO guidelines. All traced contacts will be monitored over a period of two weeks, while those who develop suspected symptoms will then be subjected to confirmatory laboratory investigation.

While research efforts continue on a global and local level to determine the modes of transmission of MERS-CoV infection, the Ministry of Public Health advises citizens and residents who suffer from chronic diseases to avoid direct contact with camels and to wash hands with soap and water thoroughly. Also MOPH recommends to implement respiratory hygiene and cough etiquette with the need to boil camel milk before drinking.

MOPH proclaimed that Health Protection & CDC Hotlines 66740948 & 66740951 are accessible 24/7 to respond to any notification or enquiry related to infectious diseases.

EID Journal: Revisiting The Oseltamivir Effectiveness Debate

Credit Wikipedia

 
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Over the past 10 years we've been witness to both the repeated demonization and the resultant defense (by public health agencies) of the neuraminidase inhibitor (NAI) antiviral oseltamivir, better known as Tamiflu(c).


The British press, in particular, have excoriated the drug using hyperbolic headlines such as the Daily Mail's: Ministers blew £650MILLION on useless anti-flu drug.

Fueling this media frenzy have been a number of Cochrane group analyses that found insufficient evidence that oseltamivir substantially reduces seasonal influenza complications in healthy adults. 

And for mild to moderate seasonal influenza - in healthy adults - the advantages of taking the drug do appear to be modest at best.  A reduction, on average, of less than a day of symptoms.

But in severe influenza, the benefits have been far more pronounced. 

The problem is, while robust Randomized Controlled Trials (RCTs) exist for mild influenza, they do not (and ethically, cannot) be mounted for severe, life threatening flu.  We are therefore left to draw our conclusions based on less rigorous, yet still compelling, observational data. 

• The Study: Antivirals Saved Lives Of Pregnant Women strongly suggested that Tamiflu was life saving for some patients with pandemic flu.
• In BMJ: Efficacy of Oseltamivir In Mild H1N1,a study suggested oseltamivir significantly reduced pneumonia among otherwise healthy pandemic H1N1 patients.
• In Study: The Benefits Of Antiviral Therapy During the 2009 Pandemic we looked at a meta-analysis of 90 observational studies that found NAIs - principally oseltamivir - initiated within 48 hours of onset, reduced the likelihood of severe outcomes by 49 to 65%.
• And most impressively . . .in Study: Antiviral Therapy For H5N1, out of 308 H5N1 cases studied, the overall survival rate was a dismal 43.5%.  But . . . of those who received at least one dose of Tamiflu . . .  60% survived . . .  as opposed to only 24% who received no antivirals.

Because of these (and other) studies, we’ve seen a push back by public health agencies against the negative perceptions of antivirals, and advocacy for their early use in cases of severe flu:

ECDC: Expert Opinion On Effectiveness of NAI Antivirals For Influenza

Wellcome Trust/AMS Report On Antivirals For Influenza

 

The CDC Responds To The Cochrane Group’s Tamiflu Study 

The Conversation: The Rise & Fall Of The Challenge To Tamiflu

CDC Research On Benefits Of Antivirals For Uncomplicated Influenza

 
All of which brings us to a new Perspective article published today in the EID Journal that reviews the both the existing RCT data along with an abundance of observational data, and offers some intriguing hints that oseltamivir might also modulate excess cytokine production (cytokine storm) in patients with severe flu infection.

The authors argue that the existing trials based on patients with relatively mild disease should not be used to drive policies on the treatment of severe influenza.  

I've only posted the abstract from a much larger discussion, so follow the link to read the review in full.

Volume 22, Number 6—June 2016 Perspective

Debate Regarding Oseltamivir Use for Seasonal and Pandemic Influenza

Aeron C. Hurt  and Heath Kelly 

Author affiliations: World Health Organization Collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia (A.C. Hurt); University of Melbourne, Parkville, Victoria, Australia (A.C. Hurt); The Peter Doherty Institute for Infection and Immunity, Melbourne (H. Kelly); Australian National University, Canberra, Australian Capital Territory, Australia (H. Kelly)

 

Abstract

A debate about the market-leading influenza antiviral medication, oseltamivir, which initially focused on treatment for generally mild illness, has been expanded to question the wisdom of stockpiling for use in future influenza pandemics. 

Although randomized controlled trial evidence confirms that oseltamivir will reduce symptom duration by 17–25 hours among otherwise healthy adolescents and adults with community-managed disease, no randomized controlled trials have examined the effectiveness of oseltamivir against more serious outcomes. 

Observational studies, although criticized on methodologic grounds, suggest that oseltamivir given early can reduce the risk for death by half among persons hospitalized with confirmed infection caused by influenza A(H1N1)pdm09 and influenza A(H5N1) viruses. However, available randomized controlled trial data may not be able to capture the effect of oseltamivir use among hospitalized patients with severe disease. 

We assert that data on outpatients with relatively mild disease should not form the basis for policies on the management of more severe disease.

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