Saturday, June 16, 2018

Clinical & Epidemiological Characteristics of A(H9N2) Infection In A Young Child - China, 2017


At first glance, H9N2 - a ubiquitous (at least in Asia and the Middle East, and recently reported in Africa), low pathogenic avian influenza (LPAI) virus that  generally produces mild symptoms in poultry - appears fairly tame. 
We've seen no large outbreaks in humans - only a few dozen widely scattered, usually mild infections over the past 20 years - mostly reported from China, Egypt, and Bangladesh (see FluTrackers Global Cumulative H9N2 Partial Case List 1998-2017).
Despite all of that, H9N2 is regarded as having at least some pandemic potential (see CDC IRAT SCORE), and so several candidate vaccines have been developed over the years.

Avian H9N2 virus occupies a special spot in our bird flu coverage because - while so far only an LPAI virus in poultry - its internal genes routinely make up the backbone of many of the HPAI viruses (including H5N1, H5N6, and H7N9) that pose the greatest risks to both poultry, and human health.
H9N2's reach extends beyond just avian flu subtypes, as we've also seen evidence of it reassorting with other influenza viruses, including A Canine H3N2 Virus With PA Gene From Avian H9N2 - Korea and PNAS: Reassortment Of H1N1 And H9N2 Avian viruses.
In 2014, in PLoS Path: Genetics, Receptor Binding, and Transmissibility Of Avian H9N2 researchers found evidence of Chinese H9N2 viruses binding preferentially to alpha 2,6 receptor cells -  the type commonly found in the human upper respiratory tract - rather than to alpha 2,3 receptor cells which are found in the gastrointestinal tract of birds.

Also in 2014  The Lancet carried a report entitled Poultry carrying H9N2 act as incubators for novel human avian influenza viruses  where  researchers warned that `reassortment between the prevalent poultry H9N2 viruses (providing genetic segments) and the influenza virus from wild birds could make the influenza evolve to adapt to domestic hosts.'
Earlier this year, in H9N2 Adaptation In Minks, we saw even more evidence of mammalian adaptation of H9N2, in a study that found H9N2 influenza virus isolated from minks has enhanced virulence in mice.
While relatively few human infections have been reported, we've seen a decided uptick in the past few years.  Although this is likely due to better surveillance, its (generally) mild presentation probably means most cases go undetected. 

We've a case report of a 2017 infection from China - one which was reported by the WHO in their 27 September 2017 Monthly Risk Assessment - albeit without much in the way of details:
Since the last update, one laboratory-confirmed human cases of A(H9N2) virus infection was reported to WHO from China. The patient is a child who had mild illness onset of 18 September, received outpatient care and had no apparent exposure history to live poultry.
Today we learn more about the case, along with some surprising statistics  about just how spotty surveillance is in China when it comes to detecting mild, novel flu virus infections.   I've only included some excerpts, so you'll want to download the PDF to read the report in its entirety.

Clinical and epidemiological characteristics of a young child infected with avian influenza A (H9N2) virus in China
First Published June 13, 2018 Case Report

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Three cases of the avian influenza A (H9N2) virus have been documented in Changsha, which is a large city that has nine districts and a population of 7.04 million in central South China. Among these patients, one was a girl and two were boys. The ages of the patients were 9 months, 2 years, and 15 years. Two cases of H9N2 were detected in September, 2015 and one was detected in 2017.

Two patients were children who had not reached the age for kindergarten and one was a student. These three cases were all mild and were detected in a sentinel hospital of the Chinese Influenza Surveillance System. We describe the clinical and epidemiological features of the youngest patient with H9N2 in 2017 and the surveillance results of the H9N2 virus in live poultry markets in Changsha.
From January 2014 to December 2017, 4212 samples were collected in live poultry markets in Changsha, among which 25.81% (1087/4212) were H9N2-positive. Public health concerns should be addressed for emerging H9N2 virus infection, and more strategies should be performed before this virus mutates to be more transmissible and highly pathogenic.


The patient, who lives in a six-person family in District A in Changsha, was a 9-month- old boy with no vaccination history of influenza vaccine and no other disease history. The boy had symptoms of fever (no temperature measurement was taken at this time) and was sneezing at 4:00 h on 18 September, 2017. Several hours later, with an auxiliary temperature of 39.5 C, he was sent to the paediatric emergency department of a sentinel hospital of the CISS system. 
A routine blood examination showed that the white blood cell count was 10.31 Â 10 9 /L and neutrophils represented 45.9% of blood cells. A throat swab sample was collected at the emergency department for pathogenic detection. Influenza virus antigen detection showed a positive result for influenza A.

Consequently, he was diagnosed with influenza and treated with oseltamivir and ibuprofen. However, the patient’s symptoms did not improve after treatment. He returned to hospital three times since 16:00 h on 18 September to 15:00 h on 20 September. Besides oseltamivir and ibuprofen, he was then prescribed oral medi-
cine, including Bifidobacterium and a Chinese traditional medicine (Xiao’er Chiqiao Qingre Keli), as well as intravenous medicine, including andrographolide injection, vitamin C, amino acids, potassium chloride, and a paediatric electrolyte supplements injection. No symptoms were observed after 15:00 h on 20 September.
The result of a throat swab sample (collected on 18 September) was H9N2-positive by using polymerase chain reaction, which was performed in the influenza surveillance network laboratory in Changsha Center for Disease Control and Prevention on 22 September. Another throat swab sample that was collected on 23 September was H9N2-negative when tested on 24 September.
        (Continue . . . )

While this child did not have recent poultry exposure, his parents both worked at a retail market where poultry was sold, and his father and sister both reported mild, non-specific symptoms in the days leading up to his illness. Again from the report:
The patient’s elder sister developed a mild fever, which rapidly disappeared between 16 and 17 September. She did not receive any medical treatment during these days. The patient’s father had mild nasal obstruction, which rapidly disappeared on 18 September. The other family members did not have any symptoms of the upper respiratory tract or influenza-like illness before the patient’s illness onset date.

Blood samples were pulled from the father and sister on the 23rd, but came back negative for H9N2.  There is no mention of additional testing for H9N2 among the remainder of the 36 close contacts identified, none of whom were reportedly symptomatic.

From the discussion section of the case report, we get a much better idea of the limits of routine testing of flu samples in China.  
Because of the mild symptoms, children infected with H9N2 and other subtypes of avian influenza virus were commonly detected by sentinel hospitals of the CISS system. However, a large amount of hospitals are not covered by this system. In Changsha, there are more than 50 hospitals, excluding private clinics and health care centres, but only two hospitals are included in the CISS system.
The authors conclude by writing:
Although no environmental surveillance evidence of our case was provided to show a full transmission chain, the positive rates of H9N2 were high in live poultry markets in nine districts of Changsha. Owing to the high prevalence of H9N2 virus in live poultry markets, more H9N2 viral infections might be missed in China. Therefore, public health concerns should be addressed for emerging H9N2 virus infection, and more strategies should be performed before this virus mutates to be more transmissible and highly pathogenic.

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

Unfortunately, the two regions of the world where these human infections tend to occur (China & Egypt) are also among the least likely to publicize their existence.

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