BackgroundWhile 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 FindingsData 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/SignificanceThe 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.

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.

HIV infection is associated with increased risk of cardiovascular complications, the underlying mechanism of which remains unclear. Plasma levels of the coagulation biomarker D-dimer (DD) correlate with increased mortality and cardiovascular events in HIV-infected patients. We compared the incidence of cardiovascular lesions and the levels of the coagulation markers DD and thrombin antithrombin in pathogenic SIV infections of rhesus and pigtailed macaques (PTMs) and in nonpathogenic SIV infection of African green monkeys (AGMs) and sooty mangabeys. Hypercoagulability and cardiovascular pathology were only observed in pathogenic SIV infections. In PTMs infected with SIV from AGMs (SIVagm), DD levels were highly indicative of AIDS progression and increased mortality and were associated with cardiovascular lesions, pointing to SIVagm-infected PTMs as an ideal animal model for the study of HIVassociated cardiovascular disease. In pathogenic SIV infection, DD increased early after infection, was strongly corre- IntroductionThere are increasing data demonstrating the significant impact of non-AIDS-defining comorbidities on the outcome of HIV infection. Cardiovascular disease (CVD) emerged as a major comorbidity during the era of highly active antiretroviral therapy (HAART), 1-3 especially in urban African-American and Hispanic populations, which are disproportionately affected by HIV and are also at high risk for CVD. CVD may be intrinsically related to HIV infection 2 or to long-term HAART, which may increase CVD risk by adverse metabolic effects (lipid changes) or vascular toxic effects. 3 To date, however, our understanding of the relationship among HIV infection, HAART, and CVD risk is unclear and incomplete, and this is a critical barrier preventing interventions that may reduce CVD mortality in these patients.CVD complications in HIV-infected subjects include thrombotic micrangiopathy (TMA), arteriopathy, dilated cardiomyopathy, abnormal coronary artery pathology (including atherothrombotic disease), and myocarditis. [4][5][6][7][8][9][10][11][12] Abnormally high levels of coagulation markers, endothelial activation markers, and platelet activation markers have also been documented in HIV-infected patients. [13][14][15] The SMART (Strategies for Management of AntiRetroviral Therapy) study confirmed that a mild-to-moderate hypercoagulable state exists in HIV infection. 2 This study also showed that increased levels of the coagulation biomarker D-dimer (DD) are associated with increases in inflammation markers (ie, IL-6), both being strongly linked to the loss of HIV/SIV control, disease progression, and death, 2 suggesting a causal relationship between immune activation/inflammation and CVD in HIVinfected patients.It is widely accepted that immune activation levels more accurately predict HIV disease progression to AIDS and death than do levels of viral replication or CD4 ϩ T cells. [16][17][18] This paradigm is supported by data from our group and others showing that natural hosts of SIV such as African green m...

Human infections of H5N1 highly pathogenic avian influenza virus have continued to occur in

Damage to the intestinal mucosa results in the translocation of microbes from the intestinal lumen into the circulation. Microbial translocation has been proposed to trigger immune activation, inflammation, and coagulopathy, all of which are key factors that drive HIV disease progression and non-HIV comorbidities; however, direct proof of a causal link is still lacking. Here, we have demonstrated that treatment of acutely SIV-infected pigtailed macaques with the drug sevelamer, which binds microbial lipopolysaccharide in the gut, dramatically reduces immune activation and inflammation and slightly reduces viral replication. Furthermore, sevelamer administration reduced coagulation biomarkers, confirming the contribution of microbial translocation in the development of cardiovascular comorbidities in SIV-infected nonhuman primates. Together, our data suggest that early control of microbial translocation may improve the outcome of HIV infection and limit noninfectious comorbidities associated with AIDS.

Although none of the participants in our study had virologically confirmed H7N9 infection, the high proportion of poultry workers with serologic evidence of H7N9 infection between May and December 2013 suggests a substantial risk of mild H7N9 infections in this group, supporting stricter control measures in live poultry markets.

BackgroundMainland China experienced pandemic influenza H1N1 (2009) virus (pH1N1) with peak activity during November-December 2009. To understand the geographic extent, risk factors, and attack rate of pH1N1 infection in China we conducted a nationwide serological survey to determine the prevalence of antibodies to pH1N1.Methodology/Principal FindingsStored serum samples (n = 2,379) collected during 2006-2008 were used to estimate baseline serum reactogenicity to pH1N1. In January 2010, we used a multistage-stratified random sampling method to select 50,111 subjects who met eligibility criteria and collected serum samples and administered a standardized questionnaire. Antibody response to pH1N1 was measured using haemagglutination inhibition (HI) assay and the weighted seroprevalence was calculated using the Taylor series linearization method. Multivariable logistic regression analyses were used to examine risk factors for pH1N1 seropositivity. Baseline seroprevalence of pH1N1 antibody (HI titer ≥40) was 1.2%. The weighted seroprevalence of pH1N1 among the Chinese population was 21.5%(vaccinated: 62.0%; unvaccinated: 17.1%). Among unvaccinated participants, those aged 6-15 years (32.9%) and 16-24 years (30.3%) had higher seroprevalence compared with participants aged 25–59 years (10.7%) and ≥60 years (9.9%, P<0.0001). Children in kindergarten and students had higher odds of seropositivity than children in family care (OR: 1.36 and 2.05, respectively). We estimated that 207.7 million individuals (15.9%) experienced pH1N1 infection in China.Conclusions/SignificanceThe Chinese population had low pre-existing immunity to pH1N1 and experienced a relatively high attack rate in 2009 of this virus. We recommend routine control measures such as vaccination to reduce transmission and spread of seasonal and pandemic influenza viruses.

Background The fraction of persons with influenza virus infection who do not report any signs or symptoms throughout the course of infection is referred to as the asymptomatic fraction. Methods We conducted a systematic review and meta-analysis of published estimates of the asymptomatic fraction of influenza virus infections. We found that estimates of the asymptomatic fraction were reported from two different types of studies: first, outbreak investigations with short-term follow-up of potentially exposed persons and virologic confirmation of infections; second, studies conducted across epidemics typically evaluating rates of acute respiratory illness among persons with serologic evidence of infection, in some cases adjusting for background rates of illness from other causes. Results Most point estimates from studies of outbreak investigations fell in the range 4%–28% with low heterogeneity (I2=0%) with a pooled mean of 16% (95% CI: 13%, 19%). Estimates from the studies conducted across epidemics without adjustment were very heterogeneous (point estimates 0%–100%; I2=97%), while estimates from studies that adjusted for background illnesses were more consistent with point estimates in the range 65%–85% and moderate heterogeneity (I2=58%). Variation in estimates could be partially explained by differences in study design and analysis, and inclusion of mild symptomatic illnesses as asymptomatic in some studies. Conclusions Estimates of the asymptomatic fraction are affected by the study design, and the definitions of infection and symptomatic illness. Considerable differences between the asymptomatic fraction of infections confirmed by virologic versus serologic testing may indicate fundamental differences in the interpretation of these two indicators.