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Preliminary Epidemiology of HPAI A(H7N9)

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    Posted: June 02 2017 at 8:11am
CDC: Emerging Infectious Diseases

Volume 23, Number 8—August 2017


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


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.

Since the first human infections with avian influenza A(H7N9) virus were identified in early 2013 (1), mainland China has experienced 5 epidemics of human infections with A(H7N9) virus (2). As of March 31, 2017, a total of 1,336 cases of laboratory-confirmed A(H7N9) virus infections were detected; case-fatality proportion was ≈40%. The fifth epidemic began September 1, 2016, and the number of A(H7N9) virus infection cases has surged since December 2016 (2). Until recently, all human infections were with low pathogenic avian influenza (LPAI) A(H7N9) virus, which causes little or no disease in infected poultry. Risk factors for human infection with LPAI A(H7N9) virus include visiting a live poultry market (LPM) or raising backyard poultry, and mortality is higher among older adults with chronic comorbid conditions (3,4).

On February 18, 2017, the National Health and Family Planning Commission of China reported genetic sequencing results on virus isolates from 2 patients from Guangdong Province who had A(H7N9) virus infection (initially reported to the Chinese Center for Disease Control and Prevention [China CDC] in January 2017) that were consistent with highly pathogenic avian influenza (HPAI) viruses. Insertions at the hemagglutinin gene cleavage site consistent with HPAI A(H7N9) virus were confirmed by the Chinese National Influenza Center (CNIC) (5). Detection of HPAI A(H7N9) virus in LPMs in Guangdong Province was reported on February 20, 2017 (6). An additional case of HPAI A(H7N9) virus infection was identified in Taiwan in a patient with illness onset in Guangdong Province (5,7,8). To assess whether disease severity in humans has changed with HPAI A(H7N9) compared with LPAI A(H7N9) virus infection, we described the epidemiologic characteristics of cases of HPAI and LPAI A(H7N9) virus infections identified during the current fifth epidemic in mainland China.

The Study

Detection, reporting, and confirmation of HPAI A(H7N9) virus infection was the same as for LPAI A(H7N9) and HPAI A(H5N1) virus infections, as previously described (3,9,10). Since the first case of HPAI A(H7N9) virus infection was identified in 2017, genetic analyses are performed at provincial China CDC laboratories or at CNIC on respiratory specimens collected from all case-patients identified with A(H7N9) virus infection to distinguish between HPAI and LPAI A(H7N9) viruses. . Field investigations and data collection protocols for HPAI A(H7N9) cases were the same as for LPAI A(H7N9) cases (3).

We extracted information from field investigation reports and the notifiable infectious surveillance system to describe the demographic, clinical, and epidemiologic characteristics of HPAI A(H7N9) case-patients. We used descriptive statistics to compare HPAI A(H7N9) cases with all LPAI A(H7N9) cases reported throughout mainland China and with LPAI A(H7N9) cases identified in the same provinces as HPAI A(H7N9) cases during the fifth epidemic reported as of March 31, 2017. Collection and analyses of data from human infections with A(H7N9) virus were determined to be part of an ongoing public health investigation of emerging outbreaks and thus were exempt from institutional review board assessment in China (3).

Eight cases of HPAI A(H7N9) virus infection were identified from 3 provinces in southern China (Figure 1). The first 2 case-patients had illness onset on December 30, 2016, and January 5, 2017, in Guangdong Province. Additional case-patients were identified in Hunan and Guangxi provinces with illness onset during February 2017 (Figure 2). 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.

All 8 HPAI A(H7N9) case-patients were admitted to hospital a median of 2.5 days (range 0–5 days) after illness onset. All 8 case-patients received oseltamivir treatment a median of 4 days (range 1–8 days) after illness onset; 7 were admitted to an intensive-care unit, and 6 were placed on mechanical ventilation for a median of 5.5 days (range 4–7 days) after illness onset. Four case-patients died a median of 6.5 days (range 5–44 days) after illness onset, and 4 recovered and were discharged home after a median of 29 days (range 21–52 days) (Table).

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).


Our preliminary findings indicate that HPAI A(H7N9) virus infection was associated with exposure to sick and dead backyard poultry in rural areas. In the ongoing fifth epidemic in mainland China, HPAI A(H7N9) case-patients were hospitalized earlier than LPAI A(H7N9) case-patients but otherwise had similar epidemiologic characteristics and disease severity.

The small number of HPAI A(H7N9) cases limited our statistical power to detect differences in epidemiologic characteristics and disease severity between HPAI and LPAI A(H7N9) case-patients. Data were not available for all variables analyzed, including outcomes for some LPAI A(H7N9) case-patients who remained hospitalized. Our findings might suggest more rapid progression and greater disease severity for HPAI A(H7N9) case-patients, because mortality was higher and the intervals from illness onset to diagnosis and to death were shorter compared with LPAI A(H7N9) case-patients; however, these differences were not significant.

Because A(H7N9) virus circulation among poultry is ongoing in mainland China, extensive efforts are needed to prevent and control the spread of LPAI and HPAI A(H7N9) viruses among poultry, including in rural areas. Avoidance of sick or dead poultry that might be infected with HPAI A(H7N9) virus can reduce transmission of HPAI A(H7N9) virus to humans. Enhanced surveillance of HPAI and LPAI A(H7N9) viruses in poultry and humans, timely virus characterization, and ongoing assessments of the epidemiology of human infections with A(H7N9) viruses are critical to guide prevention and control efforts and to provide information on the risk of these novel influenza A viruses to public health.

Dr. Zhou is the Deputy Chief of the Branch for Emerging Infectious Diseases, Public Health Emergency Center, China CDC. Her research interests are prevention and control of emerging infectious diseases as well as pandemic influenza preparedness and response.
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China H7N9 total grows by 8; studies detail virus mutations

Reflecting continued slow decline of H7N9 avian flu cases in China, eight new illnesses were reported this week, as research teams from the country published new studies that provide an early glimpse of the epidemiology and clinical features of the highly pathogenic variant that recently emerged in poultry and is also infecting people.
New H7N9 cases

The eight latest H7N9 cases from China noted today in a regular update from Hong Kong's Centre for Health Protection (CHP) are down slightly from nine cases reported last week. Among the new batch of illnesses, six patients had known exposure to poultry, poultry markets, or mobile stalls. No deaths were reported.

All of the sick people are adults with illness onsets ranging from May 12 to May 29, and five are men.

The patients are from seven different provinces that make up a broad geographic area, which with late-season northward spread has been a unique feature of China's fifth and biggest wave of H7N9 activity, which began in October and is still under way. Affected provinces are Shandong, Anhui, Guangxi, Hebei, Hubei, Shaanxi, and Sichuan.

The CHP said the new case-patient reported from Shaanxi province, located in northern China, was probably infected in Inner Mongolia province, which a few days ago announced its first-ever local H7N9 case and had recently reported its first outbreaks in live-market poultry.

In its fifth wave, China has now reported at least 722 H7N9 cases, at least 205 of them fatal. The second-largest wave, in 2013-14, saw 319 reported cases.
Threat from sick, dead poultry

Two early-release studies published in Emerging Infectious Diseases yesterday shed more light on the new highly pathogenic strain infecting poultry, which has also been detected in some patients, raising questions about whether the illness pattern for people is different from what China has seen with the low-pathogenic version of H7N9 avian flu.

Last month, Chinese researchers reported that highly pathogenic H7N9 has a slightly increased binding preference for human airway receptors compared with the low-pathogenic form.

In one of the new studies, researchers from China and their counterparts at the US Centers for Disease Control and Prevention examined eight case-patients from three provinces in southern China (Guangdong, Hunan, and Guangxi) who had highly pathogenic H7N9 infections and compared the clinical and epidemiologic findings with patterns seen for low-pathogenic H7N9.

According to their preliminary findings, infection with highly pathogenic H7N9 was associated with exposure to sick and dead poultry in rural areas. Those patients were hospitalized earlier than those infected with low-pathogenic H7N9, but otherwise showed similar patterns and disease severity.

The researchers said the low number of highly pathogenic H7N9 cases limited their power to detect differences between the two patient groups. They said their findings might suggest more rapid disease progression and greater severity, because they saw higher mortality and shorter intervals between illness onset and death for those who were sick with the highly pathogenic virus, but the differences weren't statistically significant.
Case involves antiviral resistance

In the second report, a team from China described the clinical course and genetic findings in a 56-year-old Guangdong province man who died from a highly pathogenic H7N9 virus that showed a marker for resistance to neuraminidase inhibitors (NIs), the antiviral drugs commonly used to treat influenza.

The man, who had underlying medical conditions, got sick in early January. Before he became ill, he noticed that some of his backyard chickens were sick and dying. Some of the birds were slaughtered, cooked, and eaten by the man and his family.

Four days after symptoms began, the man was hospitalized with pneumonia and given the NI oseltamivir (Tamiflu) because of the contact he had with poultry. His condition deteriorated, and he was placed on a ventilator and given peramivir, another NI, in the intensive care unit, where he died a few weeks later.

Phylogenetic analysis of an H7N9 isolated collected on day 6 of his illness, 2 days after oseltamivir treatment began, revealed a hemagglutinin marker that suggested the virus might be highly pathogenic in poultry and was similar to mutations seen in recent human cases in Taiwan and Guangdong province.

The researchers said viruses from two other patients with the highly pathogenic H7N9 mutation also had the resistance marker, and all three patients probably acquired it after oseltamivir treatment began. They added that the mutation likely contributed to the treatment failure.

Other factors may have contributed to the man's poor outcome, the group wrote, including his underlying conditions as well as a heart attack and secondary infections from antibiotic-resistant bacteria while hospitalized.

The authors concluded that so far the clinical features don't appear different from those of earlier infections with low-pathogenic H7N9, and no evidence was seen of systemic infection. They added, however, that heightened surveillance is needed to determine the extent of the two mutations.
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