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Mild Influenza A/H7N9 Infection Among Children in Guangdong Province

Zeng, Xianqiao MSc*†; Mai, Wei MB; Shu, Bo MB§; Yi, Lina PhD*†; Lu, Jing PhD*†; Song, Tie MPH*; Zhong, Haojie MB*; Xiao, Hong PhD*; Guan, Dawei MPH*; Wu, Jie PhD*; Liang, Lijun MPH*; Monagin, Corina PhD; Zhang, Xin MPH*; Ke, Changwen MD*

The Pediatric Infectious Disease Journal: January 2015 - Volume 34 - Issue 1 - p 104–107
doi: 10.1097/INF.0000000000000492
Brief Reports
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We describe the clinical and epidemiologic characteristics of 7 children infected with A/H7N9 in Guangdong Province during the winter of 2013–2014. Our results indicate that the mild or asymptomatic characteristics common in H7N9-infected children could pose challenges to our surveillance system becoming a hidden threat to the public health of China and the world.

From the *Guangdong Provincial Center for Disease Control and Prevention; Guangdong Provincial Institutes of Public Health, Guangzhou; Center for Disease Control and Prevention, Zhaoqing; §Center for Disease Control and Prevention, Zhongshan, China; and Metabiota, Inc., San Francisco, CA.

Accepted for publications June 25, 2014.

This work was supported by (1) 12th five-year-major-projects of China’s Ministry of Public Health. Grant 2012zx10004-213 (2) the PREDICT Surveillance Animal-Human Interface Project of GVF. Grant Gvf: 06-09-057-02. Benefitted from intellectual developments (or contributions) from the PREDICT project of the US Agency for International Development (USAID) Emerging Pandemic Threats Program.

The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the CDC.

The authors have no funding or conflicts of interest to disclose.

Address for correspondence: Changwen Ke, MD, Guangdong Provincial Center for Disease Control and Prevention, San Francisco, CA. E-mail: kecw2011@sina.com.

Outbreak of a novel avian-origin reassorted influenza A (H7N9) virus in China initially emerged in early 2013, causing 132 infections with 32 mortalities through 8th May.1,2 Immediately after the first dramatic appearance of the virus at March 2014 around the Yangtze River delta region, it entered a “silent stage” before re-emerging again in an outbreak in Guangdong province during the winter of 2013–2014.

Unlike A(H1N1)pdm09 and the standard seasonal influenza virus H3N2 that both have a low mortality rate, the proportions of deaths among novel H7N9 infections reached 3 0%.2 The majority of laboratory confirmed cases were found in patients with serious acute illness while only several mild/moderate infections were identified in younger adults, indicating that seriousness of infection may be linked to the patient's age.3,4

Here, we describe the epidemiologic and clinical characteristics of all cases of child infections with A/H7N9, as of February 10, 2014, in Guangdong province. These findings will provide increased insight into the body’s response against H7N9 infection in children, which also benefits the early diagnosis of the disease. Moreover, the mild/asymptomatic symptoms of infected children could pose certain challenges to influenza surveillance systems. A surveillance system that is not vigilant and does not include mild/asymptomatic illness, could possibly miss new reassortants with interpersonal transmission capacity.

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METHODS

Case Source and Classification

Data of the laboratory confirmed A/H7N9 child infections were all collected in Guangdong Province by a joint field investigation team comprising staff of the Centers for Disease Control and Prevention at the municipal and provincial level. The patients in this study were classified according to the means by which they were identified. For confirmed A/H7N9 cases identified by influenza-like illness (ILI) surveillance, they were categorized into cases discovered by ILI surveillance while the confirmed cases identified by surveillance of the close contacts were categorized into cases discovered by enhanced ILI surveillance. In addition, patients from temperature check at customs by border inspection and quarantine, a routine mean to prevent the cross-border transmission of novel A/H7N9 virus, were cataloged as cases of border inspection and quarantine. Case definitions, surveillance for identification of A/H7N9 cases and laboratory test assays of all the above-mentioned cases were the same as previous report.2,4

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Surveillance of Close Contacts and Environmental Samples in the Exposure Location

Close contacts were defined as individuals known to have been within 1 m, or had direct contact with respiratory secretions or fecal material, of a patient with confirmed H7N9 virus infection any time from the day before the onset of illness. Identified close contacts were monitored daily for 7 days for symptoms of illness and throat swabs were collected from those close contact cases in which symptoms developed to test for the presence of the H7N9 virus.4 Environmental specimens from poultry feces, the surfaces of epilators (machines that remove poultry feathers), surfaces of chopping/butchering blocks/boards, the surfaces of cages and from sewage on the ground were all sampled at the exposure location of laboratory confirmed patients with separate cotton-tipped swabs (Copan Italia, via perotti 10-Brescia, Italy). The swabs were then inserted into tube containing 3 mL of virus transport medium (Copan Italia). For the use of all above-mentioned human samples and personal information, written informed consents from all participants (their parents or legal guardian) involved in the research were obtained. This study was approved by the ethics committee of the Guangdong Provincial Center for Disease Control and Prevention, and was in compliance with the Helsinki Declaration.

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RESULTS

Epidemiological and Clinical Characteristics

The 7 patients, 4 of whom were males, were identified by the national sentinel surveillance system for ILI (patient numbers 1, 3 and 6), the enhanced ILI surveillance (patients 2, 5 and 7) and border inspection and quarantine (patient 4), respectively, of whom the age ranged from 2.5 to 17 years (mean, 13 years). The patients lived in 5 different cities within and beyond the Pearl River delta region, and date of symptom onset ranged from October 29, 2013 to January 31, 2014. Five of them (patients 2, 4, 5, 6 and 7) had a confirmed history of exposure to live poultry, including chicken, and patients 2, 5 and 7 were close contacts of known H7N9 patients. Apart from patient 4 who was not admitted to any medical facility, the other 6 patients visited clinics or hospitals 1 or 2 days after symptoms onset and were sent to a hospital within next 24 hours, and 1 patient within 2 days of laboratory confirmation. As on February 10th, all patients were subsequently discharged and patient 4 (who was not admitted to the hospital) displayed no symptoms 4 days after illness onset (Table 1).

TABLE 1

TABLE 1

The clinical characteristics of most patients included fever (patients 1–7), throat congestion (patients 1, 4, 5 and 7), cough and rhinorrhea (patients 1, 3, 5 and 7). Patients 1, 5 and 7 reported with an upper respiratory tract infection. All 7 patients had mild disease without requiring intensive care and none had pneumonia (Table 1). The above-mentioned symptoms were consistent with that observed in other cases of H7N9-infected children.2

Noticeably, 4 of 7 children were from family clusters. The patients 2 and 5, whose parents had a confirmed H7N9 infection with acute respiratory distress syndrome, were identified through enhanced ILI surveillance. In another family cluster, 2 cousins, patients 6 and 7, subsequently displayed symptoms of illness and were detected respectively through ILI surveillance and enhanced ILI surveillance. Yet close contact adults of these 2 patients, (ie, their parents) were confirmed negative to H7N9 infection in the laboratory tests.

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Environmental Contamination and Exposure

To better understand the patients’ exposure to the H7N9 virus, environmental samples from local poultry markets and their residence were collected and subjected to laboratory testing immediately after H7N9 cases were confirmed. Among 104 specimens collected from Zhongshan city, 26 (25%) tested positive for H7N9 while the positive rate for specimens collected from Zhaoqing city was 44.3% (62/140). The majority of positive specimens were collected from poultry feces, the surfaces of chopping/butchering boards and the surface of cages. Notably, through laboratory testing, we have also identified the H7N9 virus in cages from patients 6 and 7s’ residence, which provides strong evidence to support human infection through viral exposure.

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DISCUSSION

H7N9 infections, believed to result from exposure to live poultry, are usually characterized by acute respiratory distress syndrome and intensive care. Previous studies have suggested that the severity of H7N9 infection may be age-dependent, yet few have looked into cases of younger age, particularly child infection.2,5 Here, we have presented for the first time, epidemiological and clinical characteristics of 7 H7N9 cases of child infection in Guangdong province. Our results indicate that opposite to most serious, acute cases, all seven H7N9-infected children, with the age ranging from 2.5 to 17 years (mean, 13 years), displayed mild symptoms such as fever below 40°C, cough and throat congestion (rather than pneumonia) since illness onset. Consistent with these characteristics, the above-mentioned illness symptoms were also observed in 2 males in Shanghai (ages, 2 and 4 years old) and 1 male child 9 years old from Fujian province.2,6 Although there are reports of a 7-year-old female in Beijing with H7N9 infection suffering high fever (more than 40°C) and pneumonia, she soon recovered and did not present any illness symptoms 15 hours after being treated with Oseltamivir Phosphate,6 suggesting there may exist certain mechanisms in a child responsible for quick viral clearance and the associated mild symptoms.

Also, we speculate that sensitivity to infection in a child might be higher than that in adults in regard to H7N9 exposure, as was proven correct in A(H1N1)pdm09 infection during virus outbreak in Italy by a population serologic survey.5 And the identification of age-dependent infection, close contact adults free from infection, in 3 of 6 cases with a confirmed history of exposure to live poultry provide another supporting evidences to our hypothesis given the similar exposure history shared between adults and children. However, the limited family cluster cases in this study hinder us to further confirm this sensitivity with meaningful statistical analyses. The appearance of family clusters may also suggest the possibility of human-to-human transmission. No direct evidence to date was found and H7N9 exposure, illustrated by the high H7N9-positive rate, is still believed to be the main cause of cases in this study.

Taken together, the characteristics of mild/asymptomatic symptoms and the highly virus-contaminated environment may likely lead to underestimates of child infections, which is also referred to as the phenomena of “clinical iceberg”.2 The presentation of the 4-year-old H7N9-infected male child without any symptoms in close contact with a 7-year-old Beijing patient illustrate real challenges posed by such “clinical icebergs” for our sentinel surveillance system.6 The concerns are that in the H7N9-contaminated environment, younger children, a population at high risk for seasonal influenza, can be coinfected by both viruses. Such children with their mild/asymptomatic symptoms if not identified would become a generator as well as a hidden infective source of novel virus and hence make the epidemic more difficult to control. To avoid this, vigilance to surveillance of younger H7N9-infected cases or children among close contacts should be reinforced, and most importantly complete disinfection of high-risk environments such as poultry markets should be conducted so as to eliminate the source of infection.

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ACKNOWLEDGMENTS

We would like to thank the Guangzhou CDC, Shenzhen CDC, Zhongshan CDC, Zhaoqing CDC and Dongguan CDC for collecting and offering information of the H7N9 patient and environmental samples. This study was made possible by the generous support of the American people through the US Agency for International Development (USAID) Emerging Pandemic Threats PREDICT. The contents are the responsibility of the authors and do not necessarily reflect the views of USAID or the US Government.

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REFERENCES

1. Lin PH, Chao TL, Kuo SW, et al. Virological, serological, and antiviral studies in an imported human case of Avian Influenza A(H7N9) virus in Taiwan. Clin Infect Dis. 2014;58:242–246
2. Ip DK, Liao Q, Wu P, et al. Detection of mild to moderate influenza A/H7N9 infection by China’s national sentinel surveillance system for influenza-like illness: case series. BMJ. 2013;346:f3693
3. Cowling BJ, Freeman G, Wong HY, et al. Preliminary inferences on the age-specific seriousness of human disease caused by avian influenza A(H7N9) infections in China. Euro Surveill. 2013;18:20475
4. Li Q, Zhou L, Zhou M, et al. Preliminary report: epidemiology of the Avian Influenza A (H7N9) outbreak in China. N Engl J Med. 2013:1–11
5. Merler S, Ajelli M, Camilloni B, et al. Pandemic influenza A/H1N1pdm in Italy: age, risk and population susceptibility. PLoS One. 2013;8:e74785
6. Zhu YM. A limited understanding of hazard of influenza A virus subtype H7N9 in children. CJCP. 2013;15:409–411
Keywords:

H7N9; children cases; mild symptom; viral exposure; environmental samples

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