Clinical, virological and immunological features from patients infected with re-emergent avian-origin human H7N9 influenza disease of varying severity in Guangdong province.

BACKGROUND: The second wave of avian influenza H7N9 virus outbreak in humans spread to the Guangdong province of China by August of 2013 and this virus is now endemic in poultry in this region. METHODS: Five patients with H7N9 virus infection admitted to our hospital during August 2013 to February 2014 were intensively investigated. Viral load in the respiratory tract was determined by quantitative polymerase chain reaction (Q-PCR) and cytokine levels were measured by bead-based flow cytometery. RESULTS: Four patients survived and one died. Viral load in different clinical specimens was correlated with cytokine levels in plasma and broncho-alveolar fluid (BALF), therapeutic modalities used and clinical outcome. Intravenous zanamivir appeared to be better than peramivir as salvage therapy in patients who failed to respond to oseltamivir. Higher and more prolonged viral load was found in the sputum or endotracheal aspirates compared to throat swabs. Upregulation of proinflammatory cytokines IP-10, MCP-1, MIG, MIP-1α/ß, IL-1ß and IL-8 was found in the plasma and BALF samples. The levels of cytokines in the plasma and viral load were correlated with disease severity. Reactivation of herpes simplex virus type 1(HSV-1) was found in three out of five patients (60%). CONCLUSION: Expectorated sputum or endotracheal aspirate specimens are preferable to throat swabs for detecting and monitoring H7N9 virus. Severity of the disease was correlated to the viral load in the respiratory tract as well as the extents of cytokinemia. Reactivation of HSV-1 may contribute to clinical outcome.

Epidemiological and viral genome characteristics of the first human H7N9 influenza infection in Guangdong Province, China.

BACKGROUND: The first H7N9 human case in south of China was confirmed in Guangdong Province on August 2013, outside of the typical influenza season. For investigating the H7N9 virus source and transmission in the local community, we analyze the epidemiology and genome features of the virus isolated from the first human infection detected in Guangdong Province. METHODS: The data including medical records, exposure history and time line of events for the H7N9 patient and close contacts was collected. Variation and genetic signatures of H7N9 virus in Guangdong was analyzed using ClustalW algorithm and comparison with mutations associated with changes in biological characteristics of the virus. RESULTS: The female patient had a history of poultry exposure, and she was transferred from a local primary hospital to an intensive care unit (ICU) upon deterioration. No additional cases were reported. Similar to previous infections with avian influenza A (H7N9) virus, the patient presented with both upper and lower respiratory tract symptoms. Respiratory failure progressed quickly, and the patient recovered 4 weeks after the onset of symptoms. Genome analysis of the virus indicated that the predicted antigen city and internal genes of the virus are similar to previously reported H7N9 viruses. The isolated virus is susceptible to neuraminidase (NA) inhibitors but resistant to adamantine. Although this virus contains some unique mutations that were only detected in avian or environment-origin avian influenza A (H7N9) viruses, it is still quite similar to other human H7N9 isolates. CONCLUSIONS: The epidemiological features and genome of the first H7N9 virus in Guangdong Province are similar to other human H7N9 infections. This virus may have existed in the environment and live poultry locally; therefore, it is important to be alert of the risk of H7N9 re-emergence in China, including emergence outside the typical influenza season.

[Development and validation of risk score model for acute myocardial infarction in China: prognostic value thereof for in hospital major adverse cardiac events and evaluation of revascularization].

OBJECTIVE: To develop a simple risk score model of in-hospital major adverse cardiac events (MACE) including all-cause mortality, new or recurrent myocardial infarction (MI), and evaluate the efficacy about revascularization on patients with different risk. METHODS: The basic characteristics, diagnosis, therapy, and in-hospital outcomes of 1512 ACS patients from Global Registry of Acute Coronary Events (GRACE) study of China were collected to develop a risk score model by multivariable stepwise logistic regression. The goodness-of-fit test and discriminative power of the final model were assessed respectively. The best cut-off value for the risk score was used to assess the impact of revascularization for ST-elevation MI (STEMI) and non-ST elevation acute coronary artery syndrome (NSTEACS) on in-hospital outcomes. RESULTS: (1) The following 6 independent risk factors accounted for about 92.5% of the prognostic information: age > or =80 years (4 points), SBP < or =90 mm Hg (6 points), DBP > or =90 mm Hg (2 points), Killip II (3 points), Killip III or IV (9 points), cardiac arrest during presentation (4 points), ST-segment elevation (3 points) or depression (5 points) or combination of elevation and depression (4 points) on electrocardiogram at presentation. (2) CHIEF risk model was excellent with Hosmer-Lemeshow goodness-of-fit test of 0.673 and c statistics of 0.776. (3)1301 ACS patients previously enrolled in GRACE study were divided into 2 groups with the best cut-off value of 5.5 points. The impact of revascularization on the in-hospital MACE of the higher risk subsets was stronger than that of the lower risk subsets both in STEMI [OR (95% CI) = 0.32 (0.11, 0.94), chi2 = 5.39, P = 0.02] and NSTEACS [OR (95% CI) = 0.32 (0.06, 0.94), chi2 =4.17, P = 0.04] population. However, both STEMI (61.7% vs. 78.3%, P = 0.000) and NSTEACS (42.0% vs 62.3%, P = 0.000) patients with the risk scores more than 5.5 points had lower revascularization rates. CONCLUSION: The risk score provides excellent ability to predict in-hospital death or (re) MI quantitatively and accurately. The patients undergoing revascularization with risk score greater than 5.5 have lower incidence rates of endpoint.

Predictive factors of recurrent angina after acute coronary syndrome: the global registry acute coronary events from China (Sino-GRACE).

BACKGROUND: Many patients with acute coronary syndrome (ACS) develop recurrent angina (RA) during hospitalization. The aim of this non-randomized, prospective study was to investigate the predictive factors of RA in unselected patients with ACS enrolled in the global registry acute coronary events (GRACE) during hospitalization in China. METHODS: Between March 2001 and October 2004, enrolled were 1433 patients with ACS, including ST segment elevation myocardial infarction (662, 46.2%), non-ST segment elevation myocardial infarction (239, 16.7%) and unstable angina (532, 37.1%). The demographic distribution, medical history and clinical data were collected to investigate the predictive factors of RA by Logistic regression. RESULTS: During hospitalization 275 (19.2%) patients were documented with RA including unstable angina (53.2%), non-ST segment elevation myocardial infarction (27.5%), ST segment elevation myocardial infarction (19.3%). A comorbidity of dyslipidemia, prior angina, percutaneous coronary intervention (PCI) within 6 months was more common in patients with RA, P < 0.05. In the patients with RA, a significantly higher proportion of patients with acute pulmonary edema was observed, 23 (8.4%) versus 43 (3.7%), P = 0.001. Acute renal failure was present in 8 (2.9%) of patients with RA versus 19 (1.6%) of patients without RA, P = 0.165. Hemorrhagic events were present in 6 (2.2%) of patients with RA versus 8 (0.7%) of patients without RA, ventricular tachycardia/ventricular fibrillation events in 12 patients (4.3%) versus 22 patients (1.9%), congestive heart failure in 69 patients (25.0%) versus 94 patients (8.1%), myocardial re-infarction in 28 patients (10.1%) versus 15 patients (1.3%), P < 0.05, respectively. A lower proportion of patients with RA underwent in-hospital PCI, 687 (59.3%) versus 114 (41.5%), P = 0.000. A higher proportion of patients with RA received heparin, 260 (94.5%) versus 1035 (89.4%), P = 0.006; and beta-blockers 176 (64.0%) versus 864 (74.5%), P = 0.000. Multivarible regression analysis showed that RA was associated with prior angina (OR 2.086, 95% CI 1.466 - 2.967), in-hospital PCI (OR 0.579, 95% CI 0.431 - 0.778), in-hospital congestive heart failure (OR 2.410, 95% CI 1.634 - 3.555), myocardial re-infarction (OR 7.695, 95% CI 3.701 - 15.999), beta-blocker (OR 0.626, 95% CI 0.458 - 0.855), and heparin (OR 3.411, 95% CI 1.604 - 7.382). CONCLUSIONS: In-hospital congestive heart failure, myocardial re-infarction, prior angina history and use of heparin are stronger independent predictors of RA; beta-blockers and PCI are also important predictive factors for RA.

Gender based differences in patients with acute coronary syndrome: findings from Chinese Registry of Acute Coronary Events (CRACE).

BACKGROUND: Many studies have examined gender related differences in the presenting symptoms, management and prognosis of patients with acute coronary syndrome (ACS). Much data are available from industrialized countries, in which ACS is a major cause of morbidity and mortality, but relatively little information has been obtained from China, where an epidemic of cardiovascular disease is starting to emerge. The purpose of this study was to assess the differences in clinical practice in a national Chinese sample. METHODS: A total of 12 medical teaching hospitals participated in CRACE. Data collection began in 2001 and continued until 2004, 1301 patients with ACS were enrolled into the study. We compared the clinical demographics, different therapies and outcomes in hospitals between female and male patients with ACS. RESULTS: Patients had an average age of 63.13 years (ranging from 27 to 93 years) and 318 female and 983 male subjects were enrolled. Female subjects were older than male patients (67.23 years vs 61.80 years, P < 0.0001). The incidence of angina, heart failure, diabetes mellitus and hypertension in the female group was higher than in male group (73.6% vs 62.3%, P < 0.0001; 8.2% vs 5.7%, P = 0.031; 30.8% vs 18.6%, P < 0.0001 and 66.4% vs 56.8%, P = 0.001 respectively), but the incidence of smoking was less in the female group than in the male group (6.6% vs 66.2%, P < 0.0001). More male patients presented with ST-segment elevation myocardial infarction (STEMI) compared with female patients (48.5% vs 39%, P = 0.002). With the exception of beta-blocker administration, no differences were found among medications including aspirin, ACEI, lipid lowering agents and low-molecular-weight heparin (LMWH) between female and male patients presenting with ACS in hospitals. Compared with male patients with non-ST-segment elevation (NSTE) ACS, female subjects were more prone to receive beta-blockers (75.1% vs 63.4%, P = 0.001). Among STEMI and NSTE-ACS patients, fewer female subjects received reperfusion therapy compared with male subjects (37.1% vs 26.8%, P = 0.013 for STEMI; 53.6% vs 37.2 %, P < 0.0001 for NSTE-ACS). Recurrent angina was more often seen in the female group of patients with the whole spectrum of ACS (25% vs 14.5%, P = 0.005 for STEMI; 29.4% vs 20.2%, P = 0.001 for NSTE-ACS) as was true for patients with congestive heart failure. There was no significant difference in in-hospital death rates between the two groups with ACS (5.6% vs 7.1%, P = 0.2 for STEMI, and 2.1% vs 1.4%, P = 0.738 for NSTE-ACS). CONCLUSIONS: Female patients with ACS were older than male subjects and thus more often had concomitant diseases but less often had a history of smoking. They less often received reperfusion therapies and more often had higher in-hospital recurrent angina. However, there was no significant difference in in-hospital mortality between the female and male patients.

[Generation high yield vaccine strain wholly derived from avian influenza viruses by reverse genetics].

Highly pathogenic avian influenza A (HPAI) viruses of the H5N1 subtypes caused enormous economical loss to poultry farms in China and Southeastern Asian countries. The vaccination program is a reliable strategy in controlling the prevalence of these disastrous diseases. The six internal genes of the high-yield influenza virus A/Goose/Dalian/3/01 (H9N2), the hemagglutinin (HA) gene of A/Goose/HLJ/QFY/04 (H5N1) strain, and the neuraminidase gene from A/Duck/Germany/1215/73 (H2N3) reference strain were amplified by RT-PCR technique. The HA gene was modified by the deletion of four basic amino acids of the connecting peptide between HA1 and HA2. Eight gene expressing plasmids were constructed, and the recombinant virus rH5N3 was generated by cells transfection. The infection of chicken embryos and the challenge tests involving chickens demonstrated that the recombinant H5N3 (rH5N3) influenza virus is avirulent. The allantoic fluids of rH5N3-infected eggs contain high-titer influenza viruses with hemagglutination unit of 1:2048, which are eight times those of the parental H5N1 virus. The rH5N3 oil-emulsified vaccine could induce hemagglutination inhibition (HI) antibodies in chickens in 2 weeks post-vaccination, and maximum geometric mean HI-titer were observed 4 approximately 5 weeks post-vaccination and were kept under observation for 18 weeks. The rH5N3-vaccinated chickens were fully protected against morbidity and mortality of the lethal challenge of the H5N1 HPAI viruses, A/Goose/Guangdong/1/96 and A/Goose/HLJ/QFY/04, which had 8 years expansion and differences among multiple amino acids in HA protein. The N3 neuraminidase protein marker makes it possible to distinguish between H5N1 infected- and H5N3 vaccinated animals.