Yinzhong Shen

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.).

Clinical Findings in 111 Cases of Influenza A (H7N9) Virus Infection

BACKGROUND During the spring of 2013, a novel avian-origin influenza A (H7N9) virus emerged and spread among humans in China. Data were lacking on the clinical characteristics of the infections caused by this virus. METHODS Using medical charts, we collected data on 111 patients with laboratory-confirmed avian-origin influenza A (H7N9) infection through May 10, 2013. RESULTS Of the 111 patients we studied, 76.6% were admitted to an intensive care unit (ICU), and 27.0% died. The median age was 61 years, and 42.3% were 65 years of age or older; 31.5% were female. A total of 61.3% of the patients had at least one underlying medical condition. Fever and cough were the most common presenting symptoms. On admission, 108 patients (97.3%) had findings consistent with pneumonia. Bilateral ground-glass opacities and consolidation were the typical radiologic findings. Lymphocytopenia was observed in 88.3% of patients, and thrombocytopenia in 73.0%. Treatment with antiviral drugs was initiated in 108 patients (97.3%) at a median of 7 days after the onset of illness. The median times from the onset of illness and from the initiation of antiviral therapy to a negative viral test result on real-time reverse-transcriptase-polymerase-chain-reaction assay were 11 days (interquartile range, 9 to 16) and 6 days (interquartile range, 4 to 7), respectively. Multivariate analysis revealed that the presence of a coexisting medical condition was the only independent risk factor for the acute respiratory distress syndrome (ARDS) (odds ratio, 3.42; 95% confidence interval, 1.21 to 9.70; P=0.02). CONCLUSIONS During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).

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.

Adjuvant Corticosteroid Treatment in Adults With Influenza A (H7N9) Viral Pneumonia.

Objective:To determine the impact of adjuvant corticosteroids administered to patients hospitalized with influenza A (H7N9) viral pneumonia. Design:The effects of adjuvant corticosteroids on mortality were assessed using multivariate Cox regression and a propensity score-matched case-control study. Nosocomial infections and viral shedding were also compared. Setting:Hospitals with influenza A (H7N9) viral pneumonia patient admission in 84 cities and 16 provinces of Mainland China. Patients:Adolescent and Adult patients aged >14 yr with severe laboratory-confirmed influenza A (H7N9) virus infections were screened from April 2013 to March 2015. Interventions:None. Measurements and Main Results:The study population comprised 288 cases who were hospitalized with influenza A (H7N9) viral pneumonia. The median age of the study population was 58 years, 69.8% of the cohort comprised male patients, and 51.4% had at least one type of underlying diseases. The in-hospital mortality was 31.9%. Two hundred and four patients (70.8%) received adjuvant corticosteroids; among them, 193 had hypoxemia and lung infiltrates, 11 had chronic obstructive pulmonary disease, and 11 had pneumonia only. Corticosteroids were initiated within 7 days (interquartile range, 5.0–9.4 d) of the onset of illness and the maximum dose administered was equivalent to 80-mg methylprednisolone (interquartile range, 40–120 mg). The patients were treated with corticosteroids for a median duration of 7 days (interquartile range, 4.0–11.3 d). Cox regression analysis showed that compared with the patients who did not receive corticosteroid, those who received corticosteroid had a significantly higher 60-day mortality (adjusted hazards ratio, 1.98; 95% CI, 1.03–3.79; p = 0.04). Subgroup analysis showed that high-dose corticosteroid therapy (> 150 mg/d methylprednisolone or equivalent) significantly increased both 30-day and 60-day mortality, whereas no significant impact was observed for low-to-moderate doses of corticosteroids (25–150 mg/d methylprednisolone or equivalent). The propensity score–matched case-control analysis showed that the median viral shedding time was much longer in the group that received high-dose corticosteroids (15 d), compared with patients who did not receive corticosteroids (13 d; p = 0.039). Conclusions:High-dose corticosteroids were associated with increased mortality and longer viral shedding in patients with influenza A (H7N9) viral pneumonia.

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.

Prevalence and clinical management of cytomegalovirus retinitis in AIDS patients in shanghai, china

BackgroundCytomegalovirus retinitis is a common AIDS-associated illness, leading to blindness in up to 30% of patients. This study was to investigate the prevalence and clinical management of the cytomegalovirus retinitis associated with AIDS in a large municipality of China.MethodsClinical and laboratory data from 23 cytomegalovirus retinitis patients (35 eyes) out of 303 hospitalized AIDS individuals in a single medical center were analyzed retrospectively. Two of 23 patients were diagnosed cytomegalovirus retinitis just before hospitalization without anti-CMV therapy. Ganciclovir combined with the high active anti-retroviral therapy was installed for treatment of cytomegalovirus retinitis after diagnosis was confirmed. The data were analyzed by specialists and statistics was also applied.ResultsThe prevalence of cytomegalovirus retinitis in hospitalized AIDS patients was 7.6% in this study. The level of CD4+ T lymphocytes was correlated well with the occurrence of cytomegalovirus retinitis, showing 16.8% (19/113) (95% confidence interval: 10.4,25.0), 5.4% (3/56) (95% confidence interval: 1.1,14.9), and 1.4% (1/69) (95% confidence interval: 0.0,7.8) occurrence in the patients with CD4+ T lymphocyte counts < 50, 50~99, and 100~199 cells/μl, respectively. The mean CD4+ T lymphocyte counts was 31.7 ± 38.6 cells/μl in 23 AIDS patients with cytomegalovirus retinitis. Median CD4+ T lymphocyte count is 20 cells/μl with inter-quartile range as (5, 36). Seven patients died (11 eyes) and 16 patients (24 eyes) survived. The proportion of blindness and low vision in eyes infected with cytomegalovirus retinitis respectively was 20.8% (5/24) and 29.2% (7/24) when they were diagnosed in survivors. The ganciclovir therapy was effective in 16 patients (24 eyes). Clinical recovery of cytomegalovirus retinitis was 41.7% (10/24) and clinical improvement 58.3% (14/24). After anti-CMV treatment, the proportion of blindness or low vision was 16.7% (4/24).ConclusionsThe AIDS patients with CD4+ T lymphocyte < 50 cells/μl had increased susceptibility to cytomegalovirus associated retinitis. Cytomegalovirus retinitis is a serious disease causing blindness. The cytomegalovirus retinitis in the AIDS patients was response well to ganciclovir therapy. We should check their eyes routinely such as dilated fundus examination with an indirect ophthalmoscope in the AIDS patients with CD4+ T lymphocyte counts < 50 cells/μl.

Prevalence of hyperglycemia among adults with newly diagnosed HIV/AIDS in China

BackgroundThe prevalence of hyperglycemia among HIV-infected persons who are not receiving antiretroviral therapy is unknown. We conducted a cross-sectional survey to estimate the prevalence of hyperglycemia among Chinese adults with newly diagnosed HIV/AIDS.MethodsTwo thousand and six newly diagnosed HIV/AIDS patients from 10 provinces and municipalities in China were selected during 2009 to 2010. After an overnight fast, serum samples were collected to measure glucose concentrations. Demographics and medical histories were recorded. Factors associated with the presence of diabetes were analysed by logistic regression.ResultsAmong the 2006 patients, 75.67% were male. Median age was 40 years (range: 18–86 years). 19.99% had hyperglycemia, 9.47% had impaired fasting glucose (IFG) and 10.52% had diabetes. The prevalences of hyperglycemia, of IFG and of diabetes were 21.54%, 10.28% and 11.27% among men and 15.16%, 6.97% and 8.20% among women, respectively. The prevalence of diabetes increased with increasing age (7.00%, 13.36% and 21.21% among patients who were 18–40, 40–60, and ≥60 years of age respectively) and with decreasing CD4 count (6.74%, 8.45%, 9.69%, and 12.66% among patients with CD4 count of ≥350, 200–350, 50–200, and < 50/mm3 respectively). The prevalence of diabetes was higher among ethnic minority patients than among the Han patients (14.37% versus 9.24%). The logistic analysis showed that older age, lower CD4 count and minority ethnicity were significantly associated with an increased risk of diabetes.ConclusionsHyperglycemia is highly prevalent among Chinese adults with newly diagnosed HIV/AIDS. Older age, lower CD4 count and minority ethnicity are associated with increased risk of diabetes. All newly diagnosed HIV/AIDS individuals should be routinely evaluated for hyperglycemia.

Global concern regarding the fifth epidemic of human infection with avian influenza A (H7N9) virus in China

Since the first outbreak of human infection with avian influenza A (H7N9) virus was identified in 2013, five seasonal outbreaks have occurred in China. The fifth outbreak started earlier than usual. A sudden increase in cases of human infection with avian influenza A (H7N9) virus has been reported in China since September 2016, and the number of cases reported in this season is exceeding that reported in previous seasons. This increase in the number of new cases of H7N9 infection has caused domestic and international concern. This paper summarizes the current prevalence of H7N9 in China and it also discusses measures that China has taken to control this outbreak. This paper also describes steps China must take in the future. This paper can serve as a reference for prevention and control of H7N9 outbreaks around the world.

Prevalence of Anemia among Adults with Newly Diagnosed HIV/AIDS in China

Background The prevalence of anemia among antiretroviral-naïve HIV-infected patients in China has not been well characterized. We conducted a cross-sectional study to estimate the prevalence of anemia among Chinese adults with newly diagnosed HIV/AIDS. Methods One thousand nine hundred and forty-eight newly diagnosed HIV-infected patients in China were selected during 2009 and 2010. Serum samples obtained from each individual were collected to measure hemoglobin levels. Demographics and medical histories were recorded. Factors associated with the presence of anemia were analysed by logistic regression. Results Among the 1948 patients, 75.8% were male. Median age was 40 years (range: 18–80 years). The overall prevalence of anemia among HIV-infected patients was 51.9% (51.5% among men, 53.2% among women). The prevalences of mild anemia, of moderate anemia, of severe anemia were 32.4%, 17.0%, and 2.5%, respectively. The prevalence of anemia was higher among ethnic minority patients than among the Han patients (70.9% versus 45.9%). The prevalence of anemia increased with increasing age (49.6%, 53.5% and 60.1% among patients who were 18–39, 40–59, and ≥60 years of age respectively) and with decreasing CD4 count (14.0%, 22.4%, 50.7%, and 74.6% among patients with CD4 count of ≥350, 200–349, 50–199, and <50 cells/mm3 respectively). The logistic regression analysis showed that older age, lower CD4 count and minority ethnicity were significantly associated with an increased risk of anemia. Conclusions Anemia is highly prevalent among Chinese adults with newly diagnosed HIV/AIDS, but severe anemia is less prevalent in this population. Older age, lower CD4 count and minority ethnicity are associated with an increased risk of anemia.

T-SPOT.TB in the Diagnosis of Active Tuberculosis Among HIV-Infected Patients with Advanced Immunodeficiency

We evaluated the performance of T-SPOT.TB (a commercial interferon gamma release assay) and its accuracy for the diagnosis of active tuberculosis (TB) among HIV-infected subjects with advanced immunodeficiency. In a clinical prospective study, we assessed the performance of T-SPOT.TB for the diagnosis of active TB in HIV-infected patients with CD4 cell counts below 350 cells/mm(3) who were naive to antiretroviral and anti-TB therapies. Results were available from 147 patients, of whom 38 (25.9%) had active TB. The majority (85%) of the participants were male, with a median age of 40 years and a median CD4 cell count of 77 cells/mm(3). T-SPOT.TB yielded 15 (10.2%) indeterminate results. The indeterminate results were not associated with CD4 cell counts. However, younger patients were more likely to have an indeterminate result (OR = 0.91 per unit increase in age, p = 0.007). After excluding the indeterminate results, the sensitivity of T-SPOT.TB for the diagnosis of active TB was 37.1% and the specificity was 88.7%. The sensitivity of the T-SPOT.TB was independent of the CD4 cell count. However, its specificity was higher when used for patients with CD4 cell counts <100 cells/mm(3) when compared to patients with CD4 cell counts ≥100 cells/mm(3) (97.9% vs. 79.6%, p = 0.008). T-SPOT.TB could not be used as a routine tool to screen for active TB among HIV-infected patients with advanced immunodeficiency because of its poor performance and low sensitivity. However, it may be used as an adjunctive tool to diagnose active TB in this population due to its high specificity.