Nijuan Xiang

Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus

BACKGROUND Infection of poultry with influenza A subtype H7 viruses occurs worldwide, but the introduction of this subtype to humans in Asia has not been observed previously. In March 2013, three urban residents of Shanghai or Anhui, China, presented with rapidly progressing lower respiratory tract infections and were found to be infected with a novel reassortant avian-origin influenza A (H7N9) virus. METHODS We obtained and analyzed clinical, epidemiologic, and virologic data from these patients. Respiratory specimens were tested for influenza and other respiratory viruses by means of real-time reverse-transcriptase-polymerase-chain-reaction assays, viral culturing, and sequence analyses. RESULTS A novel reassortant avian-origin influenza A (H7N9) virus was isolated from respiratory specimens obtained from all three patients and was identified as H7N9. Sequencing analyses revealed that all the genes from these three viruses were of avian origin, with six internal genes from avian influenza A (H9N2) viruses. Substitution Q226L (H3 numbering) at the 210-loop in the hemagglutinin (HA) gene was found in the A/Anhui/1/2013 and A/Shanghai/2/2013 virus but not in the A/Shanghai/1/2013 virus. A T160A mutation was identified at the 150-loop in the HA gene of all three viruses. A deletion of five amino acids in the neuraminidase (NA) stalk region was found in all three viruses. All three patients presented with fever, cough, and dyspnea. Two of the patients had a history of recent exposure to poultry. Chest radiography revealed diffuse opacities and consolidation. Complications included acute respiratory distress syndrome and multiorgan failure. All three patients died. CONCLUSIONS Novel reassortant H7N9 viruses were associated with severe and fatal respiratory disease in three patients. (Funded by the National Basic Research Program of China and others.).

Epidemiology of Human Infections with Avian Influenza A(H7N9) Virus in China

BACKGROUND The first identified cases of avian influenza A(H7N9) virus infection in humans occurred in China during February and March 2013. We analyzed data obtained from field investigations to describe the epidemiologic characteristics of H7N9 cases in China identified as of December 1, 2013. METHODS Field investigations were conducted for each confirmed case of H7N9 virus infection. A patient was considered to have a confirmed case if the presence of the H7N9 virus was verified by means of real-time reverse-transcriptase-polymerase-chain-reaction assay (RT-PCR), viral isolation, or serologic testing. Information on demographic characteristics, exposure history, and illness timelines was obtained from patients with confirmed cases. Close contacts were monitored for 7 days for symptoms of illness. Throat swabs were obtained from contacts in whom symptoms developed and were tested for the presence of the H7N9 virus by means of real-time RT-PCR. RESULTS Among 139 persons with confirmed H7N9 virus infection, the median age was 61 years (range, 2 to 91), 71% were male, and 73% were urban residents. Confirmed cases occurred in 12 areas of China. Nine persons were poultry workers, and of 131 persons with available data, 82% had a history of exposure to live animals, including chickens (82%). A total of 137 persons (99%) were hospitalized, 125 (90%) had pneumonia or respiratory failure, and 65 of 103 with available data (63%) were admitted to an intensive care unit. A total of 47 persons (34%) died in the hospital after a median duration of illness of 21 days, 88 were discharged from the hospital, and 2 remain hospitalized in critical condition; 2 patients were not admitted to a hospital. In four family clusters, human-to-human transmission of H7N9 virus could not be ruled out. Excluding secondary cases in clusters, 2675 close contacts of case patients completed the monitoring period; respiratory symptoms developed in 28 of them (1%); all tested negative for H7N9 virus. CONCLUSIONS Most persons with confirmed H7N9 virus infection had severe lower respiratory tract illness, were epidemiologically unrelated, and had a history of recent exposure to poultry. However, limited, nonsustained human-to-human H7N9 virus transmission could not be ruled out in four families.

Human Streptococcus suis Outbreak, Sichuan, China

Streptococcus suis outbreak was associated with exposure to sick or dead pigs.

Risk Factors for Severe Illness with 2009 Pandemic Influenza A (H1N1) Virus Infection in China

BACKGROUND Data on risk factors for severe outcomes from 2009 pandemic influenza A (H1N1) virus infection are limited outside of developed countries. METHODS We reviewed medical charts to collect data from patients hospitalized with laboratory-confirmed 2009 H1N1 infection who were identified across China during the period from September 2009 through February 2010, and we analyzed potential risk factors associated with severe illness (defined as illness requiring intensive care unit admission or resulting in death). RESULTS Among 9966 case patients, the prevalence of chronic medical conditions (33% vs 14%), pregnancy (15% vs 7%), or obesity (19% vs 14%) was significantly higher in those patients with severe illness than it was in those with less severe disease. In multivariable analyses, among nonpregnant case patients aged ≥ 2 years, having a chronic medical condition significantly increased the risk of severe outcome among all age groups, and obesity was a risk factor among those <60 years of age. The risk of severe illness among pregnant case patients was significantly higher for those in the second and third trimesters. The risk of severe illness was increased when oseltamivir treatment was initiated ≥ 5 days after illness onset (odds ratio, 1.42; 95% confidence interval, 1.20-1.67). For persons <60 years of age, the prevalence of obesity among case patients with severe illness was significantly greater than it was among those without severe illness or among the general population. CONCLUSIONS Risk factors for severe 2009 H1N1 illness in China were similar to those observed in developed countries, but there was a lower prevalence of chronic medical conditions and a lower prevalence of obesity. Obesity was a risk factor among case patients < 60 years of age. Early initiation of oseltamivir treatment was most beneficial, and there was an increased risk of severe disease when treatment was started ≥ 5 days after illness onset.

Clinical Characteristics of 26 Human Cases of Highly Pathogenic Avian Influenza A (H5N1) Virus Infection in China

Background While human cases of highly pathogenic avian influenza A (H5N1) virus infection continue to increase globally, available clinical data on H5N1 cases are limited. We conducted a retrospective study of 26 confirmed human H5N1 cases identified through surveillance in China from October 2005 through April 2008. Methodology/Principal Findings Data were collected from hospital medical records of H5N1 cases and analyzed. The median age was 29 years (range 6–62) and 58% were female. Many H5N1 cases reported fever (92%) and cough (58%) at illness onset, and had lower respiratory findings of tachypnea and dyspnea at admission. All cases progressed rapidly to bilateral pneumonia. Clinical complications included acute respiratory distress syndrome (ARDS, 81%), cardiac failure (50%), elevated aminotransaminases (43%), and renal dysfunction (17%). Fatal cases had a lower median nadir platelet count (64.5×109 cells/L vs 93.0×109 cells/L, p = 0.02), higher median peak lactic dehydrogenase (LDH) level (1982.5 U/L vs 1230.0 U/L, p = 0.001), higher percentage of ARDS (94% [n = 16] vs 56% [n = 5], p = 0.034) and more frequent cardiac failure (71% [n = 12] vs 11% [n = 1], p = 0.011) than nonfatal cases. A higher proportion of patients who received antiviral drugs survived compared to untreated (67% [8/12] vs 7% [1/14], p = 0.003). Conclusions/Significance The clinical course of Chinese H5N1 cases is characterized by fever and cough initially, with rapid progression to lower respiratory disease. Decreased platelet count, elevated LDH level, ARDS and cardiac failure were associated with fatal outcomes. Clinical management of H5N1 cases should be standardized in China to include early antiviral treatment for suspected H5N1 cases.

Effectiveness of oseltamivir on disease progression and viral RNA shedding in patients with mild pandemic 2009 influenza A H1N1: opportunistic retrospective study of medical charts in China

Objective To describe the clinical features and effectiveness of oseltamivir on disease progression and viral RNA shedding in patients with mild pandemic 2009 influenza A(H1N1) virus infection. Design Opportunistic retrospective review of medical charts of patients with confirmed 2009 H1N1 identified through the national surveillance system in China from May to July 2009. Setting Under coordination of the Ministry of Health, local health departments were asked to collect medical records of confirmed patients and send them to the Chinese Centre for Disease Control and Prevention on a voluntary basis as part of the public health response. Population 1291 patients with confirmed 2009 H1N1 infection and available data for chart review. Main outcome measures Demographic characteristics, comorbidities, symptoms and signs, laboratory tests, findings on chest radiography, antiviral treatment, duration of fever, and duration of viral RNA shedding. Results The median age of 1291 patients was 20 years (interquartile range 12-26); 701 (54%) were male. The most common symptoms were fever (820, 64%), cough (864, 67%), sore throat (425, 33%), sputum (239, 19%), and rhinorrhoea (228, 18%). Of 920 patients who underwent chest radiography, 110 (12%) had abnormal findings consistent with pneumonia. Some 983 (76%) patients were treated with oseltamivir from a median of the third day of symptoms (2-4). No patients required admission to the intensive care unit or mechanical ventilation. 2009 H1N1 was shed from one day before onset of symptoms to up to eight days after onset in most (91%) patients, with a median of 5 (3-6) days of shedding after onset. Treatment with oseltamivir significantly protected against subsequent development of radiographically confirmed pneumonia (odds ratio 0.12, 95% confidence interval 0.08 to 0.18), and treatment started within two days of symptom onset reduced the duration of fever and viral RNA shedding. Conclusions Chinese patients with 2009 H1N1 infection predominantly presented with features of uncomplicated, self limiting acute respiratory illness. 2009 H1N1 might be shed longer than seasonal influenza virus. Treatment with oseltamivir was associated with a significantly reduced development of radiographically confirmed pneumonia and a shorter duration of fever and viral RNA shedding. Though these patients benefited from treatment, the findings should be interpreted with caution as the study was retrospective and not all patients underwent chest radiography.

Risk Factors for Human Illness with Avian Influenza A (H5N1) Virus Infection in China

BACKGROUND In China, 30 human cases of avian influenza A (H5N1) virus infection were identified through July 2008. We conducted a retrospective case-control study to identify risk factors for influenza H5N1 disease in China. METHODS A questionnaire about potential influenza H5N1 exposures was administered to 28 patients with influenza H5N1 and to 134 randomly selected control subjects matched by age, sex, and location or to proxies. Conditional logistic regression analyses were performed. RESULTS Before their illness, patients living in urban areas had visited wet poultry markets, and patients living in rural areas had exposure to sick or dead backyard poultry. In multivariable analyses, independent risk factors for influenza H5N1 were direct contact with sick or dead poultry (odds ratio [OR], 506.6 [95% confidence interval {CI}, 15.7-16319.6]; P<.001), indirect exposure to sick or dead poultry (OR, 56.9 [95% CI, 4.3-745.6]; P=.002), and visiting a wet poultry market (OR, 15.4 [95% CI, 3.0-80.2]; P=.001). CONCLUSIONS To prevent human influenza H5N1 in China, the level of education about avoiding direct or close exposures to sick or dead poultry should be increased, and interventions to prevent the spread of influenza H5N1 at live poultry markets should be implemented.

Risk Factors for Influenza A(H7N9) Disease—China, 2013

BACKGROUND The majority of human cases of novel avian influenza A(H7N9), which emerged in China in spring 2013, include reported exposure to poultry. However, specific host and exposure risk factors for disease are unknown, yet critical to design prevention measures. METHODS In April-June 2013, we conducted a case-control study in 8 Chinese provinces. Patients with laboratory-confirmed A(H7N9) (n = 89) were matched by age, sex, and neighborhood to controls (n = 339). Subjects completed a questionnaire on medical history and potential exposures, including poultry markets and other poultry exposure. We used conditional logistic regression to calculate matched and adjusted odds ratios (ORs) for the association of A(H7N9) virus infection with potential risk factors. RESULTS Fifty-five percent of patients compared with 31% of controls reported any contact with poultry (matched OR [mOR], 7.8; 95% confidence interval [CI], 3.3-18.8). Sixty-seven percent of patients compared with 35% of controls visited a live poultry market (mOR, 5.4; CI, 3.0-9.7). Visiting live poultry markets increased risk of infection even after adjusting for poultry contact and other confounders (adjusted OR, 3.4; CI, 1.8-6.7). Backyard poultry were not associated with increased risk; 14% of cases did not report any poultry exposure or market visit. Obesity (mOR, 4.7; CI, 1.8-12.4), chronic obstructive pulmonary disease (mOR, 2.7; CI, 1.1-6.9), and immunosuppressive medications (mOR, 9.0; CI, 1.7-47.2) were associated with A(H7N9) disease. CONCLUSION Exposures to poultry in markets were associated with A(H7N9) virus infection, even without poultry contact. China should consider permanently closing live poultry markets or aggressively pursuing control measures to prevent spread of this emerging pathogen.

Human Influenza A (H5N1) Cases, Urban Areas of People’s Republic of China, 2005–2006

We investigated potential sources of infection for 6 confirmed influenza A (H5N1) patients who resided in urban areas of People’s Republic of China. None had known exposure to sick poultry or poultry that died from illness, but all had visited wet poultry markets before illness.

The substantial hospitalization burden of influenza in central China: surveillance for severe, acute respiratory infection, and influenza viruses, 2010–2012

Published data on influenza in severe acute respiratory infection (SARI) patients are limited. We conducted SARI surveillance in central China and estimated hospitalization rates of SARI attributable to influenza by viral type/subtype.