Thursday, March 30, 2017

Eurosurveillance: Preliminary Epidemiology & Analysis Of Jiangsu's 5th H7N9 Wave













#12,355



Although China's 5th winter epidemic of H7N9 has been remarkable across the board, nowhere has this year's epidemic hit harder than in Jiangsu province, which in the last update had reported 133 new cases since October.

While we've been able to follow the number of cases being reported from China, they are usually provided with very little context.   

Recently, we have learned that a new lineage of H7N9 (Yangtze River Delta) has emerged - along with an HPAI version  (see MMWR:Increase in Human Infections with Avian Influenza A(H7N9) In China's 5th Wave) - but epidemiological details have been lacking. 


Today via the ECDC's journal Eurosurveillance, we get our first detailed look at the epidemiology of cases in Jiangsu Province, and we learn that the H7N9 continues to evolve - both genetically, and in terms of behavior.

While I urge you to read the entire report, a few highlights you'll encounter along the way include:
  • Despite better medical treatment for patients, the mortality rate remains high (30%+), and the authors report an`accelerated disease progression of H7N9 patients', which they note  `suggests that the viral pathogenicity might have become stronger'.
  • The authors also note ` . . .  increased detection rate of H7N9 in environmental samples suggests that the virus might become more resistant to high ambient temperature.' - which you may recall was a concern raised last summer (see HK CHP: Additional Details On China's July H7N9 Cases) when we saw a dozen `out of season H7N9 cases'. 
  • At least one co-infection (H7N9 & Seasonal H3N2) was observed, a fairly rare event that opens the door for potential viral reassortment (see EID Journal: Human Co-Infection with Avian and Seasonal Influenza Viruses, China for a more complete discussion). 
  • Viral analysis showed that while the virus `shared the same ancestor as earlier viruses from 2013 to 2015, but clustered in an independent clade (Figure 3), which suggested that H7N9 virus is continuously evolving.'
There's a lot to read and absorb here, so allot some time to review this paper.

Eurosurveillance, Volume 22, Issue 13, 30 March 2017
Research article
Significantly elevated number of human infections with H7N9 virus in Jiangsu in eastern China, October 2016 to January 2017

X Huo 1 2 , L Chen 2 3 , X Qi 1 2 , H Huang 1 , Q Dai 1 , H Yu 1 , Y Xia 3 , W Liu 1 , K Xu 1 , W Ma 4 , J Zhang 3 , C Bao 1

+ Author affiliations

Correspondence: Chang-jun Bao (bao2000_cn@163.com)

Citation style for this article: Huo X, Chen L, Qi X, Huang H, Dai Q, Yu H, Xia Y, Liu W, Xu K, Ma W, Zhang J, Bao C. Significantly elevated number of human infections with H7N9 virus in Jiangsu in eastern China, October 2016 to January 2017. Euro Surveill. 2017;22(13):pii=30496. DOI: http://dx.doi.org/10.2807/1560-7917.ES.2017.22.13.30496

Received:14 February 2017; Accepted:08 March 2017

Since first identified in 2013, the H7N9 virus has caused several waves of human infections in China, with a current wave including a number of patients with very severe disease. Jiangsu is one of the most impacted provinces, whereby as of 31 January 2017, the number of human infections (n = 109) in the ongoing fifth H7N9 wave has exceeded the sum of those in the four preceding ones. Ten of 13 cities in Jiangsu have been affected, and clustered infections as well as one co-infection with seasonal influenza have been observed. 


With a median age of 58 years and 74.3% (81/109) of patients being male, the characteristics of cases are similar to those in previous waves, however patients with H7N9 seem to have an accelerated disease progression. Preliminary case fatality remains above 30%. No significant viral mutations have been found in key functional loci.
Environmental H7N9 detection rate and number of days with high risk ambient temperatures were both significantly elevated during the month of December 2016 when most human infections were reported. A number of municipal governments in Jiangsu have implemented live poultry market closures to impede viral transmission to humans. A detectable decline in human infections has been observed in these municipalities and the entire province since January 2017.
 Discussion

Jiangsu province is now experiencing the fifth wave of human infections with H7N9, with a significantly elevated number of cases. Visiting live poultry markets is the main risk factor for H7N9 infection for the public, due to poultry contact in this setting or environmental contamination [15,16]. The high H7N9 virus detection rate in these sites may directly contribute to the elevated human H7N9 infections. Therefore, live poultry market closures have been suggested as an effective method to control such infections [17,18]. Accordingly, several municipal governments in Jiangsu province, including Suzhou, Wuxi and Changzhou, have implemented temporary comprehensive live poultry market closures since December 2016. Subsequently, a significant decline in human infections has been observed in these cities/municipalities, as well as province-wide since January 2017 (Figure 1). The decrease was even more evident in February (data not shown).

Many meteorological factors, such as temperature, relative humidity [7,19], specific humidity [20] and solar radiation [21], have been reported to influence influenza activity. As for H7N9, both daily minimum and daily maximum temperatures have been reported to contribute significantly to human infection, but not relative humidity [22]. Other meteorological factors have not been reported. The overall impact of ambient temperature on human infection rates with H7N9 may nevertheless also depend on the underlying level of environmental H7N9 virus contamination, as exemplified by the results in November 2016, when although temperatures appeared to be permissive to human infection, low rates were observed, coinciding with low rates of environmental contamination.
The environmental H7N9 contamination rate could be influenced by multiple factors, such as H7N9 virus infection rate of poultry for sale, and the hygiene level of the live poultry market. The interaction and correlation between temperature and other factors and their impact on human infections need to be investigated further in future studies.

Antivirals such as oseltamivir were administrated to almost all of the H7N9 patients in recent years in Jiangsu province. Furthermore, the time interval from onset of disease to antiviral administration is becoming shorter due to promoted sensitivity of clinicians. Clinicians also gained experiences in treatment, such as the rational use of ventilators and extracorporeal membrane oxygenation (ECMO). All of these measures are beneficial for the patients’ clinical outcome.
Nevertheless, an accelerated disease progression of H7N9 patients during latest waves was still observed, which suggests that the viral pathogenicity might have become stronger. In addition, the increased detection rate of H7N9 in environmental samples suggests that the virus might become more resistant to high ambient temperature.
Although no significant mutations were observed in key functional loci of the isolates from the current wave in our preliminary analyses, further work still needs to be conducted in detail. For instance, changes in the length of the neuraminidase stalk region might impact virulence [23] and residues 41V and/or 210D in the nucleoprotein (NP) protein could enhance polymerase activities and potential replication at low temperature [24].

The pandemic potential of the H7N9 virus needs to be closely watched. In humans, co-infection of this virus with seasonal influenza might provide reassortment opportunities for the emergence of a new pandemic virus. In addition, the continuous mutation and reassortment of H7N9 with other avian influenza viruses lately resulted in the identification of H7N9 isolates with characteristics of high pathogenicity to poultry, which was concerning for the poultry industry [25]. There is also a risk that H7N9 might acquire better ability of spreading from poultry to ducks and wild birds, and thus be disseminated worldwide, threatening humans in a much wider geographical range [26-28]. Therefore, it is critical to control the transmission of H7N9 virus in poultry to lower these risks.

To avoid the possibility of further adaption to human of this virus, early identification of human infections with H7N9 and early administration of neuraminidase inhibitors are critically needed. At present, the median time intervals from onset of disease to first medical consultation and from onset of disease to administration of neuraminidase inhibitors are two and six days, respectively. Efforts implementing effective rapid diagnostic kits in primary medical facilities, such as community clinics, could further promote the timeliness of diagnosis and antiviral therapy, as nearly half of the H7N9 patients first seek medical services in these facilities.

Until now, older males still account for most of the H7N9 patients. An overwhelming majority of the reported patients were severely infected and the overall case fatality remained above 30%. Live bird markets are the most common sites for the public to contact birds or bird materials which might carry H7N9 virus. With the continuous closures of live bird markets, the case number is expected to keep decreasing. In addition, the upcoming warmer weather would also deter the transmission of H7N9.
However, we should be alert that H7N9 cases might occur in areas where live bird market closures are not implemented, also because live poultry from places affected by H7N9 and with market closures, may be transferred to these areas. A full investigation of the current wave of human infections with H7N9 virus is still ongoing. This study presents timely preliminary results, including possible causes, which could help researchers in further detailed analyses.

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