Friday, June 02, 2017

EID Journal: 2 Expedited HPAI H7N9 Studies


Over the weekend I mentioned that while reports of HPAI H7N9 poultry outbreaks continue to come out of China, we'd not heard of any HPAI human infections since the first two from Guangdong Province (and 1 from Taiwan) last January.  I wrote:
Either there haven't been any, or China simply isn't differentiating between LPAI and HPAI human infections in their reporting.
From two reports published yesterday in the EID Journal, we have our answer.  There have been more, but (quite possibly due to testing delays), that information hasn't been included in China's weekly reports.
Through the end of March, a total of 8 HPAI H7N9 cases have been identified from across three provinces (Guangxi, Guangdong, and Hunan).

Since these two reports are so closely related, we'll look at both of them in this blog.  The first being:


Preliminary Epidemiology of Human Infections with Highly Pathogenic Avian Influenza A(H7N9) Virus, China, 2017

Lei Zhou, Yi Tan, Min Kang, Fuqiang Liu, Ruiqi Ren, Yali Wang, Tao Chen, et al.


We compared the characteristics of cases of highly pathogenic avian influenza (HPAI) and low pathogenic avian influenza (LPAI) A(H7N9) virus infections in China. HPAI A(H7N9) case-patients were more likely to have had exposure to sick and dead poultry in rural areas and were hospitalized earlier than were LPAI A(H7N9) case-patients.
Volume 23, Number 8 - August 2017
While it is difficult to draw any solid conclusions based on such a limited subset (n=8) of HPAI cases, several differences from LPAI infections are noticeable. The authors describe these cases as:
Of the 8 total case-patients, the median age was 57 years (range 28–71 years), and 4 (50%) were male. Most (75%) case-patients lived in rural areas, as defined previously (4), and all were exposed to poultry within 10 days of illness onset.
Five case-patients had exposure to backyard poultry, including 4 exposed to sick or dead poultry; 2 had household exposure to poultry purchased from LPMs, including 1 with poultry that were sick and died in the home; and 1 was a poultry worker who sold and slaughtered poultry at an LPM.
One cluster of HPAI A(H7N9) cases was identified in 2 adult sisters; 1 sister had household exposure to sick and dead poultry, and the other sister had exposures to sick and dead poultry at her sister’s house, to poultry brought inside her home from her sister’s house, and to her ill sister while that sister was hospitalized.

Granted, it may just be the luck of the draw, but finding a family cluster in such a small sampling is interesting.  They authors go on to compare these 8 HPAI cases to the far more more numerous LPAI infections this winter, writing:
Compared with all LPAI A(H7N9) case-patients reported during the fifth epidemic, HPAI A(H7N9) case-patients were significantly more likely to live in rural areas (88% vs. 47%; p = 0.031), have exposure to sick or dead poultry (50% vs. 16%; p = 0.037), and be hospitalized earlier (median 2.5 vs. 5 days; p = 0.032) (Table). 

 No significant differences were observed in median age, sex, prevalence of underlying chronic medical conditions, median time from illness onset to starting antiviral treatment, or proportion of patients who received oseltamivir treatment, intensive-care unit admission, or mechanical ventilation (Table).
Although the median time from illness onset to death (6.5 vs. 13 days) was shorter and the overall case-fatality proportion (50% vs. 37%) was higher for HPAI A(H7N9) case-patients than for LPAI A(H7N9) case-patients, these differences were not statistically significant (Table). 

When the analysis was restricted to the 3 provinces with HPAI A(H7N9) cases identified during the fifth epidemic, the only significant difference was a shorter median time from illness onset to death for HPAI A(H7N9) case-patients compared with LPAI A(H7N9) case-patients in Guangxi Province (5 vs. 17 days; p = 0.0192).

The authors conclude that their findings might suggest more rapid progression and greater disease severity for HPAI H7N9 patients, but based on the limited sample size available, these results were not statistically significant.

Moving on to the second study:

Human Infection with Highly Pathogenic Avian Influenza A(H7N9) Virus, China

Changwen Ke, Chris Ka Pun Mok, Wenfei Zhu, Haibo Zhou, Jianfeng He, Wenda Guan, Jie Wu, et al.


The recent increase in zoonotic avian influenza A(H7N9) disease in China is a cause of public health concern. Most of the A(H7N9) viruses previously reported have been of low pathogenicity. We report the fatal case of a patient in China who was infected with an A(H7N9) virus having a polybasic amino acid sequence at its hemagglutinin cleavage site (PEVPKRKRTAR/GL), a sequence suggestive of high pathogenicity in birds.
Its neuraminidase also had R292K, an amino acid change known to be associated with neuraminidase inhibitor resistance. Both of these molecular features might have contributed to the patient’s adverse clinical outcome. The patient had a history of exposure to sick and dying poultry, and his close contacts had no evidence of A(H7N9) disease, suggesting human-to-human transmission did not occur. Enhanced surveillance is needed to determine whether this highly pathogenic avian influenza A(H7N9) virus will continue to spread.
Volume 23, Number 8 - August 2017

After describing in detail a 40-day course of illness, culminating in the patient's death, the authors write:
No evidence of human-to-human transmissibility was apparent; family members and healthcare workers who were in contact with the patient did not have evidence of clinical disease. The HA cleavage site mutation that makes avian influenza viruses highly pathogenic in birds does not necessarily affect the transmissibility of the virus between humans.
However, unlike LPAI viruses, which are restricted to the chicken respiratory and intestinal tracts, HPAI viruses spread systemically within chicken and are likely to be found at high titer in multiple organs, including muscle. Thus, the risk for zoonotic transmission through handling or butchering infected poultry and consuming undercooked poultry is likely to increase with HPAI viruses.
In summary, we report the clinical disease progression of a patient infected with a mutant A(H7N9) virus that acquired sequence motifs similar to those found in HPAI viruses. The clinical features of human disease with this isolate did not appear to differ from previous infections with low pathogenicity A(H7N9) viruses, and the clinical and virologic evidence suggested that systemic dissemination of the virus did not occur.
The emergence of R292K in NA, which is associated with NA inhibitor resistance, probably contributed to the adverse clinical outcome. In China, heightened surveillance of A(H7N9) in humans with severe respiratory disease and poultry is needed to determine how widespread the polybasic HA cleavage sequence has become and to monitor for evidence of oseltamivir resistance.

 While we've seen no clear evidence that HPAI H7N9 poses a substantially greater threat than LPAI H7N9, there are some subtle signs worthy of our attention. 
Good research takes time, but the good news is we are likely to learn a lot more about this emerging virus over the summer.
But whether HPAI or LPAI, H7N9 remains the number one influenza pandemic threat in the world (see Updated CDC Assessment On Avian H7N9).

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