Tangkai Qi

Measles Virus Infection in Adults Induces Production of IL-10 and Is Associated with Increased CD4+CD25+ Regulatory T Cells

Despite steady progress in elimination of measles virus globally, measles infection still causes 500,000 annual deaths, mostly in developing countries where endemic measles strains still circulate. Many adults are infected every year in China, with symptoms more severe than those observed in children. In this study, we have used blood samples from adult measles patients in Shanghai and age-matched healthy controls to gain an understanding of the immune status of adult measles patients. IFN-α mRNA was reduced in patient PBMC compared with healthy controls. In contrast, gene expression and plasma production of IL-2, IL-10, and IFN-γ were elevated in patient blood. A similar cytokine profile was observed at early times when cultured PBMC were infected with a clinical isolate of measles virus. In contrast to previous studies in pediatric patients, we did not find a reduction in total CD4+ and CD8+ T cells in patient PBMC. Interestingly, we found that CD4+CD25+CD127low regulatory T cells were significantly increased in patient PBMC compared with controls. Using intracellular cytokine staining we also show that the measles virus induces IL-10-producing CD14+ and CD4+CD25+ cells in PBMC. Our results show that adult measles patients in the acute phase of the disease have a mixed Th1/Th2 type response, accompanied with severe immunosuppression of both innate and adaptive responses including suppression of type I IFN. Both regulatory T cells and plasma IL-10 may contribute to the immunosuppression.

Interferon-Gamma Release Assays for the Diagnosis of Active Tuberculosis in HIV-Infected Patients: A Systematic Review and Meta-Analysis

Background Interferon-gamma release assays (IGRAs) have provided a new method for the diagnosis of Mycobacterium tuberculosis infection. However, the role of IGRAs for the diagnosis of active tuberculosis (TB), especially in HIV-infected patients remains unclear. Methods We searched PubMed, EMBASE and Cochrane databases to identify studies published in January 2001–July 2011 that evaluated the evidence of using QuantiFERON-TB Gold in-tube (QFT-GIT) and T-SPOT.TB (T-SPOT) on blood for the diagnosis of active TB in HIV-infected patients. Results The search identified 16 eligible studies that included 2801 HIV-infected individuals (637 culture confirmed TB cases). The pooled sensitivity for the diagnosis of active TB was 76.7% (95%CI, 71.6–80.5%) and 77.4% (95%CI, 71.4–82.6%) for QFT-GIT and T-SPOT, respectively, while the specificity was 76.1% (95%CI, 74.0–78.0%) and 63.1% (95%CI, 57.6–68.3%) after excluding the indeterminate results. Studies conducted in low/middle income countries showed slightly lower sensitivity and specificity when compared to that in high-income countries. The proportion of indeterminate results was as high as 10% (95%CI, 8.8–11.3%) and 13.2% (95%CI, 10.6–16.0%) for QFT-GIT and T-SPOT, respectively. Conclusion IGRAs in their current formulations have limited accuracy in diagnosing active TB in HIV-infected patients, and should not be used alone to rule out or rule in active TB cases in HIV-infected patients. Further modification is needed to improve their accuracy.

Anti-Retroviral Therapy Decreases but Does Not Normalize Indoleamine 2,3-Dioxygenase Activity in HIV-Infected Patients

Background Indoleamine 2,3-dioxygenase (IDO), which is mainly expressed in activated dendritic cells, catabolizes tryptophan to kynurenine and other downstream catabolites. It is known to be an immune mediator in HIV pathogenesis. The impact of anti-retroviral therapy on its activity has not been well established. Methods We measured systemic IDO activity (the ratio of plasma kynurenine to tryptophan) in HIV-infected patients before and after highly active antiretroviral therapy (HAART) and its association with a microbial translocation marker, soluble CD14 (sCD14). Results Among 76 participants, higher baseline IDO activity was associated with lower CD4+ T cell counts (P<0.05) and higher plasma sCD14 levels (P<0.001). After 1 year of HAART, IDO activity decreased significantly (P<0.01), but was still higher than in healthy controls (P<0.05). The baseline IDO activity did not predict CD4+ T cell recovery after 1 year of therapy. The percentages of myeloid and plasmacytoid dendritic cells were not correlated with IDO activity. Conclusions IDO activity is elevated in HIV-infected patients, which is partially associated with microbial translocation. HAART reduced, but did not normalize the activity of IDO.

Fecal bacterial microbiome diversity in chronic HIV-infected patients in China.

The purpose of this study was to identify fecal bacterial microbiome changes in patients with chronic human immunodeficiency virus (HIV) infection in China. Bacterial 16S rRNA genes were amplified, sequenced (454 pyrosequencing), and clustered into operational taxonomic units using the QIIME software. Relative abundance at the phylum and genus levels were calculated. Alpha diversity was determined by Chao 1 and observed-species indices, and beta diversity was determined by double principal component analysis using the estimated phylogeny-based unweighted Unifrac distance matrices. Fecal samples of the patients with chronic HIV-infection tended to be enriched with bacteria of the phyla Firmicutes (47.20%±0.43 relative abundance) and Proteobacteria (37.21%±0.36) compared with those of the non-HIV infected controls (17.95%±0.06 and 3.81%±0.02, respectively). Members of the genus Bilophila were exclusively detected in samples of the non-HIV infected controls. Bacteroides and arabacteroides were more abundant in the chronic HIV-infected patients. Our study indicated that chronic HIV-infected patients in China have a fecal bacterial microbiome composition that is largely different from that found in non-HIV infected controls, and further study is needed to evaluate whether microbiome changes play a role in disease complications in the distal gut, including opportunistic infections.

Analysis of the immunologic status of a newly diagnosed HIV positive population in China

BackgroundThe immunologic status of a newly diagnosed HIV positive population in the era of antiretroviral therapy in China has not been extensively evaluated. We conducted a cross-sectional survey to evaluate the CD4 counts of newly diagnosed HIV-infected persons and determine the factors influencing these counts in China.MethodsTwo thousand eight hundred and sixty-six newly diagnosed HIV-infected patients from 10 provinces in China were selected during 2009 to 2010. Serum samples were collected to measure CD4 counts by flow cytometry. Demographics and medical histories were recorded. Multivariate logistic regression models were used to analyze factors associated with low CD4 count (<100 cells/mm3) at HIV diagnosis.ResultsAmong the 2866 patients, 2159 (75.33%) were male. Mean age was 40 years (range: 18–86 years). The median CD4 count at HIV diagnosis was 83 cells/mm3, 72.02% of the patients had a CD4 count that was ≤200 cells/mm3, 53.98% had CD4 counts <100 cells/mm3. The difference in CD4 counts between males and females was not statistically significant (P=0.469). The median CD4 count differed significantly according to age (P=0.002), province (P<0.001), ethnicity (P<0.001) and HIV transmission route (P<0.001). In multivariate logistic analysis, factors associated with greater odds of low CD4 count at HIV diagnosis included male sex, younger age, HIV transmission route classified as unknown transmission risk, having been diagnosed in provinces Guangxi, Henan, Heilongjiang, Jiangxi, Shanghai and Yunnan.ConclusionsAt the time of HIV diagnosis, a large proportion of HIV-infected patients in China had an initial CD4 count that was consistent with relatively advanced disease. Low CD4 count was associated with male gender, younger age, route of HIV transmission and geographical areas. HIV testing policy that promotes routine testing for HIV infection is needed to facilitate earlier HIV diagnosis.

Serological survey of viral hepatitis markers among newly diagnosed patients with HIV/AIDS in China

The aim of the study was to determine the seroprevalence and epidemiological features of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection among patients newly diagnosed with HIV/AIDS in China.

Prevalence of Dyslipidemia Among Antiretroviral-Naive HIV-Infected Individuals in China.

AbstractLittle is known about the epidemiological features of dyslipidemia among antiretroviral-naive HIV-infected individuals in China. We used a cross-sectional study design to estimate the prevalence of dyslipidemia in this population, and to identify risk factors associated with the presence of dyslipidemia.One thousand five hundred and eighteen antiretroviral-naive HIV-infected individuals and 347 HIV-negative subjects in China were enrolled during 2009 to 2010. Demographics and medical histories were recorded. After an overnight fast, serum samples were collected to measure lipid levels. Factors associated with the presence of dyslipidemia were analyzed by logistic regression.Mean total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL) levels were lower in HIV-positive than HIV-negative subjects, but mean triglyceride (TG) was higher in HIV-positive subjects. The overall prevalence of dyslipidemia in HIV-positive and HIV-negative groups did not differ (75.6% vs. 73.7%, P = 0.580). However, the prevalence of high TC (8.4% vs. 28.2%, P < 0.001) and high LDL (8.5% vs. 62.6%, P < 0.001) was lower in HIV-positive than HIV-negative subjects, and the prevalence of high TG (33.9% vs. 17.0%, P < 0.001) and low HDL (59.6% vs. 11.2%, P < 0.001) was higher in HIV-positive than HIV-negative subjects. Logistic analysis showed that HIV positivity was significantly associated with both an increased risk of high TG and low HDL and a decreased risk of high TC and high LDL. The mean levels of TC, of LDL and of HDL showed an increasing trend with increasing CD4 count in HIV-positive subjects. Multivariable logistic regression found that lower CD4 count was significantly associated with both an increased risk of high TG and low HDL and a decreased risk of high TC in HIV-positive subjects.Among antiretroviral-naive HIV-infected Chinese adults, there was a high prevalence of dyslipidemia characterized by high TG and low HDL, which was associated with lower CD4 counts. These data support the assessment of lipid profiles before and after initiation of antiretroviral therapy regardless of age.

Extra-pulmonary viral shedding in H7N9 Avian Influenza patients.

BACKGROUND The clinical features of avian-origin influenza virus A (H7N9) virus infection have been extensively characterized, but viral RNA detection in extra-pulmonary samples has seldom been studied. OBJECTIVES To study shedding of viral RNA in extra pulmonary samples in patients with avian influenza H7N9 infections. STUDY DESIGN A retrospective study of throat swabs, urine, fecal samples and sera collected sequentially from 18 hospitalized patients with H7N9 infections in Shanghai, China, between April and July in 2013 was conducted. RESULTS Viral RNA could be detected in urine samples from 17 patients, in fecal samples from 15 and in sera from 14 with a real-time reverse transcription polymerase chain reaction. The median duration of shedding of viral RNA was 19.7 days in throat swabs, 22 days in feces, 21.1 days in urines and 16.2 days in sera, indicating prolonged shedding of viral RNA in feces and urine compared with that in throat swabs. Prolonged duration of viral RNA detection in throat swabs and urine samples was observed in more severe patients. Moreover, in previously reported oseltamivir resistant patients, the NA gene with a 292K mutation could also be detected in their extra-pulmonary as well as in their respiratory samples. CONCLUSION Our data indicated a high frequency of viral RNA detection in feces, urine and sera in H7N9-infected patients and pointed out the potential risk of transmission.

Fatal cases of human infection with avian influenza A (H7N9) virus in Shanghai, China in 2013.

We retrospectively reviewed the medical records of 17 fatal H7N9 cases in Shanghai in 2013, analyzed clinical variables and described their clinical and epidemiologic characteristics. The median age was 73 years, and 82.4% had underlying medical conditions. The most frequent symptoms were fever (100%), followed by productive cough (47.1%) and dry cough (35.5%). Thirteen (76.5%) patients had dyspnea or respiratory distress, five (29.4%) had shock, and four (23.5%) had acute kidney injury. Seventeen (100.0%) patients had lymphopenia. Involvement of both lungs was found by chest radiography in 14 (82.4%) patients at presentation. Fifteen (88.2%) patients were hospitalized. The median times from illness onset to hospitalization and to diagnosis confirmation were both six days. Eleven (64.7%) patients were admitted to the intensive care unit. Sixteen (94.1%) patients were treated with oseltamivir. The median time from illness onset to oseltamivir treatment was six days. Among six patients for whom the duration of viral shedding was available, the median duration of viral shedding after oseltamivir treatment was 17 days. The median time from illness onset to death was 11 days. Refractory hypoxemia accounted for most deaths. The clinical and epidemiologic characteristics in the Shanghai fatal series of patients do not differ from other reports of H7N9 patients in China. This investigation reflects a delay in the diagnosis and antiviral treatment of H7N9 patients in the early stage of the epidemic in Shanghai. Late antiviral treatment and a long duration of viral shedding may be associated with a fatal outcome in these patients.

Trends in clinical characteristics of HIV-infected patients initiating antiretroviral therapy in Shanghai from 2006 to 2011

This study aimed to characterise the clinical characteristics of HIV-infected patients accessing antiretroviral therapy (ART) in Shanghai, China, from 2006 to 2011. We retrospectively reviewed the records of patients who initiated ART in Shanghai during the 6-year period of 2006 through 2011. The median age at ART initiation decreased from 41 years in 2008 to 38 years in 2011. The median CD4 counts at ART initiation rose from 65 cells/mm3 in 2006 to 203 cells/mm3 in 2011. The proportion of patients with CD4 counts <200 cells/mm3 at ART initiation decreased from 88.5% in 2006 to 49.6% in 2011. The proportion of patients starting stavudine-based regimens of stavudine/lamivudine/efavirenz and stavudine/lamivudine/nevirapine fell from 49.2% in 2006 to 23.4% in 2011. The proportion of patients starting nevirapine-based regimens of zidovudine/lamivudine/nevirapine and stavudine/lamivudine/nevirapine fell from 44.3% in 2006 to 16.5% in 2011. The study reflects that the clinical characteristics of the patients initiating ART in Shanghai have changed over time; ART was increasingly provided in patients with higher CD4 counts; and the regimens containing stavudine were prescribed less frequently. Strategies to facilitate early access to ART and further reduction in stavudine use are needed.