Early hypercytokinemia is associated with interferon-induced transmembrane protein-3 dysfunction and predictive of fatal H7N9 infection.

A unique avian-origin A/H7N9 influenza virus has so far caused 134 cases with 44 deaths. Probing the host factors contributing to disease severity, we found that lower levels of plasma inflammatory cytokines on hospital admission correlated with faster recovery in 18 patients with A/H7N9 influenza virus, whereas high concentrations of (in particular) IL-6, IL-8, and macrophage inflammatory protein-1ß were predictive of a less favorable or fatal outcome. Analysis of bronchoalveolar lavage samples showed up to 1,000-fold greater cytokine/chemokine levels relative to plasma. Furthermore, patients with the rs12252-C/C IFN-induced transmembrane protein-3 (IFITM3) genotype had more rapid disease progression and were less likely to survive. Compared with patients with the rs12252-T/T or rs12252-T/C genotype of IFITM3, patients with the C/C genotype had a shorter time from disease onset to the time point when they sought medical aid (hospital admission or antiviral therapy) and a shorter interval to development of the acute respiratory distress syndrome stage (reflected by shorter intervals between clinical onset and methylprednisolone treatments and higher rates of mechanical ventilator use), as well as experiencing elevated/prolonged lung virus titers and cytokine production and higher mortality. The present analysis provides reported data on the H7N9 influenza-induced "cytokine storm" at the site of infection in humans and identifies the rs12252-C genotype that compromises IFITM3 function as a primary genetic correlate of severe H7N9 pneumonia. Together with rs12252 sequencing, early monitoring of plasma cytokines is thus of prognostic value for the treatment and management of severe influenza pneumonia.

Clinical findings for early human cases of influenza A(H7N9) virus infection, Shanghai, China.

A novel strain of influenza A(H7N9) virus has emerged in China and is causing mild to severe clinical symptoms in infected humans. Some case-patients have died. To further knowledge of this virus, we report the characteristics and clinical histories of 4 early case-patients.

Clinical comparison of one recovered case and one fatal case of human infection with H7N9 avian influenza in Shanghai Public Health Clinical Center in China.

H7N9 avian influenza is the latest subtype of influenza virus to emerge in the world. By April 17, 2013 in Shanghai, a total of 31 confirmed cases were reported, and 11 of these patients died. The epidemiological characteristics and the clinical progress of this new human flu infection are still not clear. Thirteen confirmed patients have now been treated in Shanghai Public Health Clinical Center. Among the first batch of patients, hospitalised at the beginning of April 2013, two who were admitted with the same estimated date of onset of disease had very different outcomes. After active treatment at the Centre, one recovered by April 18, 2013, but one patient entered critical condition and died on April 11, 2013. The clinical and laboratory characteristics in hospital are here analysed and compared to learn more about H7N9 avian influenza. Confirmation that the observed differences are valuable for prognosis and treatment decisions for H7N9 patients awaits authentication by analysis of more patients.

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-alpha mRNA was reduced in patient PBMC compared with healthy controls. In contrast, gene expression and plasma production of IL-2, IL-10, and IFN-gamma 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(+)CD127(low) 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.

[Peg-interferon alfa-2a and highly active antiretroviral drug therapy on hepatitis C patients with AIDS].

OBJECTIVE: To evaluate the clinical effect and side-effect of peg-interferon alfa-2a (PEG-IFN alfa-2a) and highly active antiretroviral therapy (HAART) for patients infected with hepatitis C virus (HCV) and co-infected with human immunodeficiency virus (HIV). METHODS: Twenty-two patients with HCV/HIV co-infection received highly active antiretroviral therapy initially; after their CD4 lymphocyte counts rose to over 0.20x10(9)/L, they were separated into two groups: one group with CD4 lymphocytes over 0.35x10(9)/L (high group) and one group with CD4 lymphocytes below 0.35x10(9)/L (low group). Both groups were given 180 microg of PEG-IFN alfa-2a every week intramuscularly. HCV RNA and HIV RNA loads, blood cell and CD4 lymphocyte counts, and liver functions were routinely examined. RESULTS: After 12, 24 and 48 weeks of PEG-IFN alfa-2a therapy, mean HCV RNA loads reduced 2.0650 log10 copies/ml (t=3.8733), 2.9146 log10 copies/ml (t=7.6741) and 2.4315 log10 copies/ml (t=5.8202) from the baseline at week 0 in the 13 patients in the high group, and reduced 1.1522 log10 copies/ml (t = 2.8937), 1.4189 log10 copies/ml (t=2.4422) and 1.1167 log10 (t=1.1261) in the 8 patients of the low group. However, there was no significant difference between the early viral response rate (EVR) and the end of treatment viral response rate (ETVR) of the two groups. In the high group, the white blood cell count was lower at 24 weeks than the base line (t=2.4700), and the blood platelet count was lower both at 24 and 48 weeks than the base line (t=2.3273 and t=3.6149). CONCLUSIONS: PEG-IFN alfa-2a can effectively reduce HCV RNA loads in patients with HCV-/HIV co-infection, and the inhibition rate in patients with higher CD4 lymphocyte counts is better. The EVR and ETVR of the two groups of patients show similar results after the treatment. PEG-IFN alfa-2a can reduce the white blood cell counts and the blood platelet counts in the peripheral blood.

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.

Prognosis of 18 H7N9 avian influenza patients in Shanghai.

PURPOSE: To provide prognosis of an 18 patient cohort who were confirmed to have H7N9 lung infection in Shanghai. METHODS: Patients' history, clinical manifestation, laboratory test, treatment strategy and mortality were followed and recorded for data analysis. RESULTS: A total of 18 patients had been admitted into Shanghai Public Health Clinical Center from April 8th to July 29, 2013. 22.2% of the patients were found to have live poultry contact history and 80% were aged male patients with multiple co-morbidities including diabetes, hypertension and/or chronic obstructive pulmonary disease (COPD). This group of patients was admitted to the clinical center around 10 days after disease onset. According to laboratory examinations, increased C reactive protein (CRP), Procalcitonin (PCT), Plasma thromboplastin antecedent (PTA) and virus positive time (days) were indicative of patients' mortality. After multivariate analysis, only CRP level showed significant prediction of mortality (P = 0.013) while results of prothrombin time (PT) analysis almost reached statistical significance (P = 0.056). CONCLUSIONS: H7N9 infection induced pneumonia of different severity ranging from mild to severe pneumonia or acute lung injury/acute respiratory distress syndrome to multiple organ failure. Certain laboratory parameters such as plasma CRP, PCT, PTA and virus positive days predicted mortality of H7N9 infection and plasma CRP is an independent predictor of mortality in these patients.

Analysis of the clinical characteristics and treatment of two patients with avian influenza virus (H7N9).

Avian influenza is one of the most dangerous contagions in poultry worldwide, and avian influenza A viruses are the major pathogens responsible. Outbreaks of H7N9, a strain of the avian influenza A virus H7 subtype, have increasingly been reported in several countries since 2007. This spring, H7N9 broke out in China and has thus far caused 24 cases of infection and 7 deaths. Recently, we treated two patients with H7N9 infection. The infection was characterized by respiratory symptoms, fever, rapid progression, and significant hypoxemia. Laboratory tests showed a low level or decrease in leukocytes, a drop in blood platelets, and an increase in myocardial enzymes and aspartate aminotransferase. Oseltamivir, anti-infective drugs, and immunoglobulin were administered. Supplemental oxygen or non-invasive mechanical ventilation helped to relieve symptoms. This report provides information on the clinical characteristics and treatment of two Chinese patients with H7N9.

[Effect of moxibustion on immunological function in the patient of AIDS of spleen-kidney yang-deficiency].

OBJECTIVE: To observe the therapeutic effect of moxibustion on AIDS patients of spleen-kidney yang-deficiency. METHODS: Sixty-six cases of AIDS were divided into a treatment group and a control group, 33 cases in each group. All of the patients were treated with HAART, with moxibustion at Tianshu (ST 25), Shenque (CV 8), Zhongwan (CV 12), Guanyuan (CV 4) added in the treatment group for 3 months. Clinical symptoms and cell immunity were recorded before and after treatment. RESULTS: After treatment, the effective rate was 90.9% in the treatment group, which was better than 66.7% in the control group (P < 0.05). The improvement of the score for clinical symptoms in the treatment group was superior to that in the control group (P < 0.01). After treatment, the CD4 lymphocyte counts increased in the two groups, with no significant difference between the two groups (P > 0.05). Additionally, increase of total lymphocyte count in the treatment group was superior to that in the control group (P < 0.05). CONCLUSION: Moxibustion can increase the therapeutic effect of HAART on AIDS patients and increase the total lymphocyte count.