南海官兵所驻岛礁甲、乙、丙和戊型肝炎病毒调查研究

目的了解我国南海官兵所生活岛礁的甲、乙、丙和戊型肝炎病毒分布情况。评估感染风险度,制定预防措施。方法 (1)上礁前,采集158名将上岛守礁官兵血清样本,进行常规肝炎病毒检测。(2)无菌采集上述158名上岛礁3个月后官兵的血液样本和礁上物体表面生理盐水样本390份,共548份。收集后保存于-20℃冰柜中,立即随补给船送回实验室进行乙型肝炎病毒DNA和甲、丙、戊型肝炎病毒RNA检测。结果 (1)158名守礁官兵上礁前检出血清甲肝抗体(lgG)阳性5人(3.16%);乙肝病毒表面抗原、丙肝和戊型肝炎抗体检测均为阴性。(2)上礁3个月以后,158份血清样本检出甲肝抗体阳性7份(4.43%),其中lgG阳性5份,lgM阳性2份(甲肝RNA为阳性);乙肝DNA检测有2份阳性(1.27%)。丙肝和戊型肝炎病毒RNA均为阴性。390份礁上的物体表面样本:检出甲、丙、戊肝病毒RNA阳性分别为24份(6.15%)、3份(0.77%)、2份(0.51%);乙肝病毒DNA阳性5份(1.28%)。结论守礁官兵所驻岛礁生活环境中存在甲、乙、丙、戊肝传染源,卫生部门要提高认识,有效地控制传染源,培养官兵良好的生活习惯,切断传染途径,预防守礁官兵病毒性肝炎传播和流行,并制定相应的病毒性肝炎流行治疗预案,配备治疗药品。     

两种免疫程序下的抗体动力学曲线分析

目的通过分析抗体产生及其动力学变化的规律,为制备高效价血清提供参照。方法将EV71灭活病毒和HAV灭活病毒按照两种免疫程序注射新西兰兔,检测其在不同时间段的免疫血清效价。结果加强免疫2d后抗体效价有明显的下降,之后逐步升高并在5～7d时到达一个新的峰值,且每周加强一次与每2周加强一次所得到的抗体效价基本一致。结论再次免疫后,抗体水平的升高并非是呈光滑的曲线式上升,而是呈折线式上升;获得高效价的免疫血清,需通过3次加强免疫,再次免疫的间隔时间以一周为宜,在第3次加强7d后可收集血清,整个免疫过程应在8周内完成。     

围产期妇女静脉血及脐血甲、乙丙型肝炎病毒和艾滋病病毒感染调查

本文总结１９９６－１９９９年连续４年分批随机抽样对２８０名临床妇女静脉血和脐血行ＥＬＩＳＡ法检测甲型肝炎病毒（ＨＡＶ）、乙型肝炎病毒（ＨＢＶ）、丙型肝炎病毒（ＨＣＶ）、艾滋病病毒（ＨＩＶ）感染调查。结果：５６３份血样中,ＨＢＶ感染率达４５％、５０％。ＨＡＶ、ＨＣＶ、ＨＩ（Ｖ感染率为０。提示：ＨＢＶ感染仍为目前监测防治重点。     

人源抗-HAV Fab真核表达载体的构建及表达

目的 构建人源抗－ＨＡＶＦａｂ真核表达载体并进行表达。方法 采用ＤＮＡ重组技术将抗体重轻链基因与信号肽基因连接,并分别插入真核表达载体ｐＣｄｈｆｒｌ、ｐＣＤＮＡ３．１;以脂质体介导法转染ＣＨＯ细胞,经Ｇ４１８筛选细胞,ＥＬＩＳａｂ基因的表达。结果 成功地构建了Ｆａｂ表达载体。转染细胞后,经ＥＬＩＳＡ检测,细胞增养上清中有抗原结合活性的Ｆａｂ片段。结论Ｆａｂ真核表达载体的构建及其在ＣＨＯ细胞中的表达     

Prolonged Gut Dysbiosis and Fecal Excretion of Hepatitis A Virus in Patients Infected with Human Immunodeficiency Virus

Hepatitis A virus (HAV) causes transient acute infection, and little is known of viral shedding via the duodenum and into the intestinal environment, including the gut microbiome, from the period of infection until after the recovery of symptoms. Therefore, in this study, we aimed to comprehensively observe the amount of virus excreted into the intestinal tract, the changes in the intestinal microbiome, and the level of inflammation during the healing process. We used blood and stool specimens from patients with human immunodeficiency virus who were infected with HAV during the HAV outbreak in Japan in 2018. Moreover, we observed changes in fecal HAV RNA and quantified the plasma cytokine level and gut microbiome by 16S rRNA analysis from clinical onset to at least 6 months after healing. HAV was detected from clinical onset up to a period of more than 150 days. Immediately after infection, many pro-inflammatory cytokines were elicited, and some cytokines showed different behaviors. The intestinal microbiome changed significantly after infection (dysbiosis), and the dysbiosis continued for a long time after healing. These observations suggest that the immunocompromised state is associated with prolonged viral shedding into the intestinal tract and delayed recovery of the intestinal environment.     

胶州湾菲律宾蛤仔甲型肝炎病毒污染调查及对策研究

为查明胶州湾菲律宾蛤受ＨＡＶ污染情况，于１９９１．７～１９９２．８月间，在湾内设６个监测点，每月定时、定点采集标本共７５份。经核酸斑点杂交试验，ＨＡＶ分离及ＰＣＲ法检测ＨＡＶ前体ＲＮＡ，结果表明：胶州湾的一定海域，一定时间的菲律宾蛤有ＨＡＶ污染迹象，但已失去生物活性。同时流行病学调查证实，菲律宾蛤不是青岛市区甲型肝炎（甲肝）发病和流行的直接原因。但鉴于市民生活污水直接排入胶州湾内，必须加强市区生活污水治理和对市民食用海产品的饮食卫生教育。     

Inactivation of hepatitis a virus by heat treatment in aqueous solution

Hepatitis A virus infections have been reported recently among hemophilic patients in Italy and Germany, leading to speculation that infectious hepatitis A virus (HAV) might have been present in some factor VIII concentrates. In both cases, the implicated factor concentrates had been treated by a solvent/detergent method, which inactivates enveloped viruses but which would not be expected to inactivate HAV, a nonenveloped picornavirus. To determine whether HAV would be inactivated during pasteurization of factor VIII concentrate, an alternative method employed for virus inactivation, we determined the extent to which the infectivity of cell culture-adapted HAV, suspended either in cell culture medium or in a proprietary stabilizing buffer, was reduced by heat treatment at 60°C for 10 hr. The titer of infectious HAV declined rapidly at 60°C, but the stabilizer considerably delayed HAV inactivation. In cell culture medium, HAV was inactivated by >3.6 log₁₀ within 30 min, but 3.6 log₁₀ inactivation of HAV was reached only after 6 hr in the presence of the stabilizer. Residual infectious HAV was present after even 10 hr of heat treatment in the stabilizer, indicating that <5.2 log₁₀ infectious HAV particles are inactivated under these conditions. In the presence of the stabilizer, HAV was significantly more stable than poliovirus type 1, which has been used to validate virus inactivation by pasteurization. We conclude that pasteurized factor VIII concentrate should pose little if any risk for transmission of HAV if pooled plasma used for its manufacture contained low levels of the virus.     

Hepatitis A antibody titres after infection and immunization: implications for passive and active immunization

Titres of antibodies against hepatitis A virus (HAV) were determined in patients, in donors, and in volunteers after active, passive, and combined immunization. Highest titres were found in recently infected persons: in 109 IgM anti-HAV positive persons, the geometric mean titre (GMT) was 15,400 mlU/ml. The GMT in 265 anti-HAV positive blood donors was 10,700 mlU/ml. The anti-HAV seroprevalence in 19,746 donors increases with age: at the age of 40 years, 50% have antibodies. Titres after active, passive, and combined immunization were studied in three groups: 51 persons received inactivated HAV vaccine at months 0, 1, and 6. The GMT after the booster was 3,400 mlU/ml at month 7. All persons produced more than 100 mlU/ml anti-HAV. Forty-nine persons received both 5 ml immunoglobulin and three vaccinations, yielding a GMT of 1,300 mlU/ml at month 7. One person in this group produced less than 100 mlU/ml anti-HAV. Forty-nine persons received 5 ml immunoglobulin intramuscularly. At day 5 the GMT was 96 mlU/ml. The estimated minimum protective level (10 mlU/ml) was reached in 3 months. Hepatitis A vaccination may supersede the use of immunoglobulin as prophylaxis for travellers to endemic areas. Passive immunization remains necessary for protection during outbreaks. The dosage regimen for passive immunization is based on old studies using preparations with unknown anti-HAV content. Concern regarding the antibody levels in immunoglobulin preparations is justified; the prevalence of HAV antibodies in developed countries continues to fall. Our results indicate that dosage regimens should be reconsidered. Dosage should be deduced logically from the anti-HAV antibody content of the immunoglobulin preparation. © 1993 Wiley-Liss, Inc.