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Clinical features of six sporadic cases of infant pulmonary hemorrhage of enterovirns 71 infection without skin rash

Shijun HE ; Airong HUANG ; Yimei JIN ; Dong CHEN ; Haomei YANG ; Chuanxia WANG ; Aihua ZHOU ; Xia WANG ; Miaomiao LIN

Chinese Journal of Infectious Diseases.2009;27(12):749-752. doi:10.3760/cma.j.issn.1000-6680.2009.12.010

Objective To understand the clinical features of infant pulmonary hemorrhage of enterovirus 71 infection without skin rash, and to improve the diagnosis and treatment of this disease.Methods Six infants infected with enterovirus 71 and presented pulmonary hemorrhage but no skin rash between November 2007 and October 2008 were retrospectively reviewed. The clinical manifestations, clinical outcomes, treatments, laboratory data and chest imaging changes of the cases were analyzed. Results The 6 cases were all younger than 2 years old. The cases distributed throughout the whole year without peak season. Enterovirus 71 gene was detected by reverse transcription-polymerase chain reaction (RT-PCR) and real time polymerase chain reaction from throat swabs and secretions of the respiratory tract. All the cases began with fever, and 4 of which were accompanied with vomit, and 2 accompanied with cough. After 1 to 3 days, they all got sudden deterioration, manifested with pale and cyanosis, and 1 had hyperspasmia. After intubation, they all had pink frothy fluid from the endotracheal tube. They all had obvious hyperglycaemia, 4 had tachycardia, and 2 had hypertension. All the 6 cases died, and 4 died within 6 h after deterioration. Conclusions Pulmonary hemorrhage of enterovirus 71 infection without skin rash is seen in infants. It is sporadic throughout the whole year. The disease is fulminant and the case often dies in short period of time.

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Study on high incidence of hepatitis C and its epidemiological features in Jianping county, Liaoning Province

Zongfen LI ; Yiping FENG ; Lianzheng YU ; Li LIU ; Liya YU ; Liying XING ; Lixia HE ; Guowei PAN

Chinese Journal of Infectious Diseases.2009;27(12):746-748. doi:10.3760/cma.j.issn.1000-6680.2009.12.009

Objective To investigate the significantly elevated incidence of hepatitis C and mortality of cirrhosis and hepatocellular carcinoma (HCC) in Jianping county, and to explore the epidemiological features. Methods The data from database of death registry and infectious disease surveillance in Jianping county, Liaoning Province were analyzed. The distributions of incidence of hepatitis B and hepatitis C, mortality of cirrhosis and HCC in 23 villages and towns were investigated.Spearman's correlation was used to explore the correlations between hepatitis, cirrhosis and HCC.Results The standardized mortality of HCC in males and females in Jianping county were 77. 6/10~5and 22. 0/10~5, respectively, which were 2. 0 and 1. 7 times, respectively of the average levels of Liaoning rural areas. The incidence of hepatitis C was 58. 0/10~5 , which was 9. 5 times of the averagelevel of Liaoning Province. There were positive correlations between incidence of hepatitis C and mortality of cirrhosis (r=0. 495, P = 0. 008), and mortality of cirrhosis and HCC (r=0. 646, P<0.01). Conclusions The incidence of hepatitis C and mortality of cirrhosis and HCC in Jianping county are significantly higher than the average levels of Liaoning Province. Further investigations of the suspected causes are needed.

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The expression and function of retinoic acid-inducible gene Ⅰ in monocyte-derived dendritic cells in patients with hepatitis B virus infection

Gangde ZHAO ; Qing XIE ; Hui WANG ; Baoyan AN ; Huijuan ZHOU ; Nina JIA ; Lanyi LIN ; Cuicui SHI ; Qing GUO ; Hong YU

Chinese Journal of Infectious Diseases.2009;27(12):727-732. doi:10.3760/cma.j.issn.1000-6680.2009.12.005

Objective To investigate the expression and function of retinoic acid-inducible gene Ⅰ(RIG-Ⅰ) in monocyte-derived dendritic cells (MoDC) at different stages of hepatitis B virus(HBV)infection and to explore the role of RIG-Ⅰ in the disease progression after HBV infection. Methods Peripheral blood samples were collected from 28 hepatitis B virus-infected persons, including 21 cases of chronic hepatitis B (CHB) and 7 of acute hepatitis B (AHB). Eighteen healthy subjects were recruited as controls. Purified CD14~+ monocytes were isolated by CD14 microbeads. MoDCs were induced from CD14~+ monocytes with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4 for 7 days, and then were infected with vesicular stomatitis virus (VSV) to stimulate RIG-Ⅰ expression. The mRNA expression levels of RIG-Ⅰ, interferon (IFN )-promoter stimulating factor-1 (IPS-1) and IFN-β at 16 hours and 24 hours after infection with VSV were measured by real-time quantitative polymerase chain reaction (PCR). Data with normal distribution were tested by analysis of variance. Continuous variables between groups were compared using Mann-Whitney U test. Comparison among multiple groups was done by Kruskal-Wallis test. Results The expression levels of RIG-Ⅰ in MoDCs from CHB patients were significantly lower than those in AHB patients and healthy controls at 16 hours (2.44±2.03, 19. 54±3. 15, 21. 48±8. 39, respectively; F=7.451,P=0.002) and 24 hours (2. 68±2. 93, 10. 31 ±3. 88, 14. 01 ±5. 04, respectively, F = 7. 908, P = 0. 001)following VSV stimulation. The IPS-1 levels in both CHB patients and AHB patients were higher than those in healthy controls at 16 hours (2. 05±l. 08, 1. 99±1. 56, 0. 60±0. 31, respectively) F=7.246,P =0.003) and 24 hours (2. 27±2. 16, 3.24 ± 1.21, 1. 08±0. 73, respectively; F= 13. 598, P = 0. 001).Furthermore, the IFN-β expression levels were significantly lower in CHB patients compared to AHB patients and healthy controls at 16 hours and 24 hours after VSV stimulation. Conclusions The expressions of RIG-Ⅰ and IPS-1 in MoDC are abnormal in HBV infected persons, which indicates that RIG-Ⅰ signaling pathway might be blocked by HBV. The impaired function of MoDC may play a role in HBV infection and chronicity.

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Investigation of viremia persistence time in genotype 4 hepatitis E virus infection

Yihan LU ; Anqun HU ; Yingjie ZHENG ; Yiyun TAN ; Fadi WANG ; Xinsen YU ; Qingwu JIANG

Chinese Journal of Infectious Diseases.2009;27(9):535-539. doi:10.3760/cma.j.issn.1000-6680.2009.09.006

Objective To determine the persistence time of genotype 4 hepatitis E (HE) viremia after the onset of clinical symptoms in HE patients and provide essential data for study on HE epidemiologieal transmission, so that to evaluate potential contagiousness of HE patients after clinical stage. Methods The first serum samples from 162 HE patients after hospitalized in Eastern China were collected and tested for hepatitis E virus (HEV) RNA by nested reversed transcription- polymerase chain reaction (RT-PCR). The persistence time of HEV viremia after the onset of clinical symptoms was estimated with Kaplan-Meier survival analysis. Results HEV RNA was detectable in 101 out of 162 serum samples with positive rate of 62.35%, which was all grouped to genotype 4 by homology analysis. Furthermore, HEV RNA was detectable in 74 (64.91%) out of 114 male and 27 (56.25%) out of 48 female, which was not significantly different (χ2 = 1.08, P=0. 30). Kaplan-Meier survival analysis showed that the median persistence time of HEV genotype 4 viremia was 24 days after the onset of clinical symptoms (95% CI: 18-30 days), which meant that the viremia of 50% HE patients remaining detectable up to 24 days after the onset. The 75% and 25% percentiles were 14 days and 31 days, respectively. There was no significant difference of viremia persistence time between male and female (Breslow test: P=0.98, Tarone-Ware test: P=0.91). Conclusions The viremia of 75% patients with HEV genotype 4 infection could persistent until 2 weeks after the onset of clinical symptoms and that of some patients could persistent over 1 month. It is indicated that the viremia is still persistent and HE patient could be a reservoir even after the clinical symptoms disappeared and biochemical marks normalized.

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Discrepancy analysis between clinical diagnosis and pathological diagnosis in patients with chronic hepatitis B

Chinese Journal of Infectious Diseases.2009;27(9):527-530. doi:10.3760/cma.j.issn.1000-6680.2009.09.004

Objective To analyze the discrepancy between clinical diagnosis and pathological diagnosis in patients with chronic hepatitis B (CHB) and explore more objective criteria of clinical diagnosis. Methods Three hundred and nineteen CHB patients received liver biopsy for pathological assessments were investigated retrospectively in this study. The discrepancy between clinical diagnosis and pathological diagnosis was analyzed. The data were compared using nonparametrie test. Results Based on the standard of pathological diagnosis, accuracies of clinical diagnosis with mild, moderate, severe CHB and cirrhosis were 67.3%, 37.6%, 2.7% and 23.5%, respectively, and the misdiagnose rate of cirrhosis was as high as 93.4 0%. Coincidence rates of clinical diagnosis of fibrosis staging inmild, moderate and severe CHB were 75.0%, 81.7% and 83.8%, respectively, which were relatively high, but was as low as 23.5% in cirrhosis. Levels of alanine aminotransferase (ALT) and total bilirubin(TBil) were not gradually increasing with stages of mild, moderate, severe and cirrhosis in clinical or pathological diagnosis. Conclusions There are differences between clinical diagnosis and pathological diagnosis. The accuracies of clinical diagnosis are low in patients with severe hepatitis and cirrhosis. It's better to make diagnosis based on liver biopsy so that to improve the diagnose accuracy.

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Construction, prokaryotic expression and immunogenic analysis of HXB2 subtype Tat mutant of human immunodeficiency virus type-1

Cunmei LI ; Songhua DENG ; Jie CAO ; Jinghong WANG ; Lu CHEN ; Desheng HUANG ; Wei PAN

Chinese Journal of Infectious Diseases.2009;27(9):517-521. doi:10.3760/cma.j.issn.1000-6680.2009.09.002

Objective To construct shifting mutant of cysteine-rich region to 3?@terminal of Tat gene of human immunodeficiency virus type-1 (HIV-1) HXB2 strain, and to analyze the immunogenicity of mutant protein (Tat-cct) after prokaryotically expressed and purified. Methods The cysteine-rich region (nucleotides 64--111) of Tat gene was shifted to 3'terminal of Tat of HIV-1 HXB2 strain by polymerase chain reaction (PCR) and Tat mutant DNA sequence was obtained. Prokaryotie express plasmid pET32a-Tat-cct was constructed and transformed into E. coli BL21 (DE3), then Tat-cct protein was expressed and purified. BALB/c mice were immunized with the fusion protein Tat-cct, and immunogenicity of the immunized serum was detected by enzyme-linked immunosorbent assay (ELISA). Results The recombinant plasmid pET32a-Tat-cct expressed in E. coli BL21 (DE3) and the relative molecular mass of the purified fusion protein was 31 000. The serum antibody titer of mice immunized with Tat-cct recombinant protein was 1 : 1600, which binded specifically with both Tat-ect protein and Tat protein (amino acids 1-101). Conclusions The recombinant protein Tat-cct of Tat mutant strain can be expressed efficiently in E. coli and well retains immunogenicity, which provides valuable information for basic research of HIV-1 Tat vaccine.

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Clinical analysis of 21 patients with multisystemic invasive fungal diseases

Feifei YANG ; Liping ZHU ; Yuxian HUANG ; Shu CHEN ; Weimin JIANG ; Jiming ZHANG ; Guangfeng SHI ; Xinhua WENG

Chinese Journal of Infectious Diseases.2009;27(9):543-546. doi:10.3760/cma.j.issn.1000-6680.2009.09.009

Objective To investigate the clinical features, diagnosis, treatment and prognosis of muhisystemic invasive fungal diseases. Methods Twenty-one patients with multisystemic invasive fungal diseases who were hospitalized in department of infectious diseases from January 2001 to June 2008 were retrospectively reviewed. The pathogenic bacteria, involved organs, underlying diseases, clinical manifestations, treatments and prognoses of muhisystemic invasive fungal diseases were analyzed. Results Among 21 recruited cases, 17 had underlying diseases and 11 were treated with long-term immunosuppressive agents. The main pathogenic bacteria were Cryptococcus neoformans, Aspergillus and Candida parapsilosis. Lung and brain were involved in 16 cases (skin involve in 2 cases and lymph node involved in 1 case simultaneously), lung and lumbar involved in 2 cases, heart valves involved in 2 cases, and liver, spleen and bone marrow involved in 1 case. Eight cases were cured, 6 were improved and 7 died. Conclusions In this study, most of the 21 cases with multisystemic invasive fungal diseases are immunocompromised. The main pathogenic bacterium is Cryptococcus neoformans. The lung and brain are common organs involved. Prognosis is associated with early diagnosis and active anti-fungal treatment.

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Mycological profile of cryptococcal meningitis in patients with non-acquired immune deficiency syndrome during treatment and follow-up

Yuanjie ZHU ; Junyong ZHANG ; Julin GU ; Jianghan CHEN ; Hang XU ; Jin ZHAO ; Yun QIU ; Hai WEN

Chinese Journal of Infectious Diseases.2009;27(9):540-542. doi:10.3760/cma.j.issn.1000-6680.2009.09.008

Objective To examine mycological profile of eryptococcal meningitis in patients with non-acquired immune deficiency syndrome (AIDS) during treatment and follow-up so that to support clinical therapy. Methods Data of 28 cuhure-confirmed cryptoeoccal meningitis patients with non-AIDS were retrospectively analyzed. Fungat smear, count, culture and latex agglutination test of cerebrospinal fluid (CSF) were done during treatment and follow-up. Initial treatment included intravenous amphotericin B plus oral flucytosine or f;uconazole for at least 6 weeks, and consolidation treatment included oral fluconazole and (or) itraeonazole for at least 2 months. All 28 patients were cured. The data were analyzed by rank-sum test. Results The positive rate of CSF fungal smear was 92.9% before treatment and gradually decreased, and the fungal count was significantly reduced over time after treatment. While fungal smears of some patients were still positive after initial treatment. Fungal growth time in culture was gradually extended, and fungal culture turned to be negative in all patients after 2 weeks of treatment. The positive rate of latex agglutination test of CSF was 100%. Cryptococcal antigen titer decreased steadily after treatment, which was not correlated with the decrease of fungal count. Conclusion Mycological tests of patients with eryptococcal meningitis should be interpreted comprehensively during treatment, and result of each test should be specifically analyzed.

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The relationship between macrophage migration inhibitory factor and chronic hepatitis B and hepatitis B virus-related cirrhosis

Ka ZHANG ; Yaomin DU ; Qihuan XU ; Xin SHU ; Lubiao CHEN ; Ni CHEN ; Gang LI ; Qiuxiong LIN

Chinese Journal of Infectious Diseases.2009;27(9):531-534. doi:10.3760/cma.j.issn.1000-6680.2009.09.005

Objective To investigate the level of serum macrophage migration inhibitory factor (MIF) and its correlation with serum precollagen Ⅲ peptide (PⅢP) and tissue inhibitor of metalloproteinase (TIMP)-1 in patients with chronic hepatitis B (CHB) and hepatitis B virus (HBV)-related cirrhosis. Methods Forty-four CHB patients (hepatitis B group), 44 patients with HBV-related cirrhosis (cirrhosis group) and 30 healthy controls (control group) were enrolled in this study. The venous blood was collected and MIF level was detected by enzyme-linked immunosorbent assay (ELISA). Correlations between MIF and PⅢP, TIMP-1 were analyzed in observed groups. Comparison between groups was done using t test. The correlations between MIF level and alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), plasma thromboplastin antecedent (PTA), PⅢP and TIMP-1 were analyzed by rectilinear correlation. Results The levels of serum MIF, PⅢP and TIMP-1 in CHB group and cirrhosis group were all significantly higher than those in control group (t=12.87,5.28, 10.98,t=11.22,14.84,11.17;all P<0.05), while there were no significant differences between CHB group and cirrhosis group (t= -1.05,1.52,--2.07;all P>0.05). There was no correlation between MIF level and ALT, AST, TBil and PTA. MIF level in CHB patients with hepatitis B e antigen (HBeAg) positive and high viral load were both higher than that in patients with HBeAg negative and low viral load. MIF level was both positively correlated with PⅢP level in CHB group and cirrhosis group (r=0. 603, P<0.05 and r=0. 415, P<0. 05, respectively). MIF level was also positively correlated with TIMP-1 level in CHB group (r=0. 458, P<0.05), while not correlated in cirrhosis group (r=0. 210, P>0.05). Levels of PⅢP and T1MP-1 were both correlated in CHB group and cirrhosis group (r=0. 849, P< 0.05 and r=0. 424, P<0.05, respectively). Conclusions The levels of serum MIF are significantly increased both in patients with CHB and cirrhosis. The early production of MIF might be related with viral replication, but not with liver function. MIF participates in formations of hepatitis, liver fibrosis and cirrhosis, which could reflect the degree of liver cirrhosis.

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Follow-up study on the etiology of acute hepatitis B in adults

Dongliang LI ; Xiaohui MIAO ; Qianli MIAO ; Shumin ZHAO ; Yong HAO ; Lei WANG ; Fang HE ; Baihua TANG

Chinese Journal of Infectious Diseases.2009;27(9):522-526. doi:10.3760/cma.j.issn.1000-6680.2009.09.003

Objective To understand the etiology of acute hepatitis B (AHB) in adults and investigate the mechanisms of hepatic injury and viral clearance in AHB. Methods One hundred and twenty adult AHB patients were enrolled. Epidemiological and clinical data were collected from the case history records or face-to-face inquiry, and serum samples were collected during hospitalization and follow-up. To observe dynamic patterns of AHB etiology, the markers of hepatitis B virus (HBV) were detected by enzyme-linked immunosorbent assay (ELISA); the level of HBV DNA and HBV genotype were determined by real-time polymerase chain reaction (PCR). Enumeration data were analyzed by non-parametric rank sum test. Comparison between groups was done by t test and that between rates of samples was done by Pearson χ2 test. Results Serum HBV DNA was positive in 48.33% of patients at the time of diagnosis with mean level of 9.84×04 copy/mL, and became undetectable after 12.5 days on average. The median levels of serum alanine aminotransferase (ALT) were 1600 U/L and 1490 U/L in HBV DNA positive and negative groups, respectively (z=-0. 678, P=0. 498). However, the mean levels of serum ALT were (2058±123) U/L and (1393±139) U/L in groups of HBV DNA<1×104 copy/mL and>1×104 copy/mL, respectively, which was significantly different (t=-2.17, P=0. 049). Genotype B accounted for 52.5%, genotype C 42.5 and genotype B and C mixed type 5.0% in 58 patients with HBV DNA positive. Eight patterns of serum HBV markers were presented at first visiting. HBsAg(+), HBeAg(+), anti-HBc(+), anti-HBc IgM(+) and HBsAg(+), anti-HBe(+), anti-HBc(+), anti-HBc IgM(+) were the most common patterns, which accounted for 38.3% and 30.0%, respectively. The dynamic patterns of serum HBV markers of 28 AFIB patients were prospectively followed up. The rate of serum FIBsAg loss was 100. 0% and the median time of negative-conversion was 3 weeks. The cumulative positive rate of anti-HBs was 85.7% after 52 weeks of follow-up. The rate of serum HBeAg loss was 100.0%. HBeAg was negative in 53.6% of patients at first visiting and the rest of patients achieved negative within 4 weeks after onset. The positive rate of anti-HBe was 82.1% during 52 weeks of follow-up. Total anti-HBc (including IgG and IgM) was keeping positive in all patients within 52 weeks, and the negative rate of anti-HBc IgM was 39. 3% after followed up for 52 weeks. Conclusions Rapid HBV clearance andserum HBV marker conversion are significantly different between AHB and chronic hepatitis B.

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