Sunday, June 26, 2016

Differences In Poultry Exposure Between Human H7N9 and H5N1 Infection


While H7N9 remains very much an avian influenza virus - and in 2014 a Chinese case-control study pegged exposure to birds at live bird markets as the biggest risk factor (see CDC: Risk Factors Involved With H7N9 Infection) - there have been subtle hints that other routes of transmission might be at work as well.

During the first two winter epidemics (spring of 2013 & 2014), the Chinese government won deserved praise for providing a good deal of detail on each and every case.

Daily updates were provided with the patient's age, gender, location, date of onset, likely exposures, condition, and even the number of close contacts being followed up on. 

That welcomed openness ended abruptly very early in 2015, and since then the timeliness, and level of detail, of China's avian flu reporting has diminished significantly (see H7N9: No News Is . . . . Curious).  

While we don't know the reasons behind this shift in reporting policy, we were starting to see subtle signs of clustering - and fewer direct links with poultry being cited -  around the time their detailed reporting ended.

A couple of examples:
First the EID Journal: Nosocomial Co-Transmission Of H7N9 & H1N1pdm09 which involved 2 patients at a hospital in Zhejiang Province in 2014, and then in NEJM: Probable Hospital Cluster of H7N9 - China, 2015, we saw a cluster involving a patient and two doctors, again in Zhejiang Province.

And then there were the studies (see Lancet: Clinical Severity Of Human H7N9 Infection) that estimated the actual number of symptomatic H7N9 cases in China were likely anywhere from 10 to 200 times greater than had been officially reported.

Although both are endemic in China's poultry, in the 3+ years since H7N9 emerged, China has officially reported more than 780 H7N9 cases, but they've only reported 10 H5N1 cases.

Even if one assumes both viruses are seriously under reported in the human population, the ratio of 78 to 1 strongly suggests H7N9 is better adapted to infecting humans than is H5N1.

And that raises some interesting questions about how the transmission dynamics of the H7N9 virus in China might differ from H5N1.

Which brings us to a analysis recently published in Epidemiology & Infection that finds (among admittedly sparse data) that poultry contact was far more commonly reported with Chinese H5N1 infection than with H7N9.

Epidemiol Infect. 2016 Jun 7:1-8. [Epub ahead of print]

Quantified degree of poultry exposure differs for human cases of avian influenza H5N1 and H7N9.

Bethmont A1, Bui CM1, Gardner L2, Sarkar S3, Chughtai AA1, Macintyre CR1.

Preliminary evidence suggests that direct poultry contact may play a lesser role in transmission of avian influenza A(H7N9) than A(H5N1) to humans.

To better understand differences in risk factors, we quantified the degree of poultry contact reported by H5N1 and H7N9 World Health Organization-confirmed cases. We used publicly available data to classify cases by their degree of poultry contact, including direct and indirect. To account for potential data limitations, we used two methods: (1) case population method in which all cases were classified using a range of sources; and (2) case subset method in which only cases with detailed contact information from published research literature were classified.

In the case population, detailed exposure information was unavailable for a large proportion of cases (H5N1, 54%; H7N9, 86%). In the case subset, direct contact proportions were higher in H5N1 cases (70·3%) than H7N9 cases (40·0%) (χ 2 = 18·5, P < 0·001), and indirect contact proportions were higher in H7N9 cases (44·6%) than H5N1 cases (19·4%) (χ 2 = 15·5, P < 0·001).

Together with emerging evidence, our descriptive analysis suggests direct poultry contact is a clearer risk factor for H5N1 than for H7N9, and that other risk factors should also be considered for H7N9.

The H7N9 virus is constantly changing, and has evolved into at least 48 genotypes in China (see Nature: Dissemination, Divergence & Establishment of H7N9 In China).

Over the past 18 months we've seen several studies that have documented changes in the behavior of H7N9 since it first emerged.

In 2015's EID Journal: The Transmission Potential Of A(H7N9) In China, the authors found that while no evidence of sustained transmission was detected, they noted:

  • `evidence of a small but significant amount of transmission between humans in the first and second waves’
  • `evidence of increased transmission potential in the second wave
While last month, in EID Journal: Human Infection With H7N9 During 3 Epidemic Waves - China, researchers found patients hospitalized in the 2nd and 3rd wave with severe H7N9 tended to be younger, and from more rural areas, than those from the 1st wave.

They also found that the risk of death among hospitalized patients was greater in the second and third waves, although that varied between provinces.

Exactly why the demographics of the later outbreaks have changed is a much tougher question to answer, although the authors suggest:

The increased risk in waves 2 and 3 might imply a changing pathogenesis associated with genetic clades of H7N9 virus that appeared in later epidemic waves or differences in clinical management in different provinces, although case ascertainment bias could not be ruled out.

Although the case-control study performed in 2013 citing live bird exposure as the #1 risk factor was probably valid, the H7N9 viruses circulating in China today have had 3+ years to evolve, adapt, and diversify.

And the H7N9 viruses that turn up next fall may well have learned some new tricks over the summer.  So it is important to track any changes in their behavior.
While the recent reduction in H7N9 cases reported over the few months merits some guarded optimism, the lack of detailed reporting out of China - along with the co-circulation of so many dangerous HPAI viruses (H5N1, H5N6, H10N8, etc.) - continues to give pause.

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