慢性肝炎交叉感染的临床对比分析

目的研究慢性乙型肝炎重叠甲型肝炎与乙型肝炎重叠戊型肝炎患者在临床表现、预后及病毒之间相互干扰方面的异同。方法慢性乙型肝炎重叠甲型肝炎组50例,慢性乙型肝炎重叠戊型肝炎组50例和单纯乙型肝炎组50例,其中每组各含4例肝硬化患者;对3组患者的临床表现实验室检查等进行对比分析。结果在症状、转氨酶及胆红素方面,重叠感染组均重于单纯慢性乙型肝炎组（P〈0.05或P〈0.01）。但与预后有关的一些指标,如白蛋白、凝血酶原活动度及病死率,两种重叠感染对慢性乙型肝炎的影响有所不同：甲型肝炎重叠感染似对慢性乙型肝炎影响不大,但戊型肝炎重叠感染似对慢性乙型肝炎有比较严重的不良影响。在病毒干扰方面,两种重叠感染似对乙型肝炎病毒复制均有一定抑制作用,戊型肝炎重叠感染更明显。结论甲型肝炎重叠感染对慢性乙型肝炎的症状、转氨酶、胆红素虽有一定影响,但对其预后无太大影响,对乙型肝炎病毒复制似有一定的抑制,但不如戊型肝炎明显;戊型肝炎重叠感染对慢性乙型肝炎的临床表现及其预后均有明显的影响,对乙型肝炎病毒的抑制也较强。     

Hepatitis E virus: neutralizing sites, diagnosis, and protective immunity

There have been increased attentions on HEV and its associated diseases in recent years as a result of an increased number of reports on autochthonous patients from many developed countries. Vaccine development and better disease management are expected from protective immunity with increased knowledge on the pathogenesis and virology of HEV. This review summarizes the current understanding of the HEV virology, the key neutralization sites (epitopes) on the surface of the viral capsid, the host humoral immune responses for HEV infection, and the protective immunity conferred by natural infection and vaccination. Recombinant VLPs were prepared to mimic the protective and neutralizing epitopes on the virion surface, thus being capable of eliciting protective immunity when injected to nonhuman primates or human volunteers during preclinical tests and clinical trials. Four markers—viral RNA, anti‐HEV IgM, anti‐HEV IgG, and low avidity of anti‐HEV IgG—are important in the diagnosis of HEV infection, particularly for patients presenting with acute hepatitis symptoms. This toolbox of genomic and immunological assays is valuable in furthering our understanding of the time course of HEV infection and the subsequent hepatitis during preclinical and clinical development of an efficacious vaccine. Two vaccine candidates had shown good tolerability, high immunogenicity, and high efficacy against symptomatic and/or asymptomatic HEV infection. One of them has been licensed in China recently. However, many issues need to be resolved before new technological progresses can benefit the people who need them most. Copyright © 2012 John Wiley & Sons, Ltd.     

Work-related support among women in caregiving occupations

The relationship of work-related support to mental and physical health was examined among a random sample of 362 women employed as social workers and licensed practical nurses. Work-related support was found to have a direct effect on employed women's mental and physical health. However, work-related support did not buffer the impact of job demands on health.     

Hepatitis A vaccines

The global disease burden associated with hepatitis A virus (HAV) is expected to increase in the coming years due to a shift in the epidemiological pattern of the disease. A decrease in the prevalence of natural immunity is leading to an increased number of adolescents and adults susceptible to a disease that is associated with greater morbidity, mortality and treatment costs in older-age groups. Current HAV vaccines have been shown to be safe, highly immunogenic and confer long-lasting protection against HAV disease. Vaccine-induced antibodies persist for more than 12 years in vaccinated adults and mathematical modeling predicts antibody persistence for more than 25 years in over 95% of vaccine recipients. However, the cost of HAV vaccines has been prohibitive for some countries. Recent studies in countries with transitioning HAV endemicity indicate that the cost-benefit ratio of mass vaccination against HAV would be similar to other routine childhood vaccinations.     

Hepatitis B immunity in teenagers vaccinated as infants: an Italian 17-year follow-up study

We assessed the persistence of hepatitis B surface antigen antibody (anti-HBs) and immune memory in a cohort of 571 teenagers vaccinated against hepatitis B as infants, 17 years earlier. Vaccinees were followed-up in 2003 and in 2010 (i.e. 10 years and 17 years after primary vaccination, respectively). When tested in 2003, 199 vaccinees (group A) had anti-HBs <10 mIU/mL and were boosted, 372 (group B) were not boosted because they had anti-HBs ≥10 mIU/mL (n = 344) or refused booster (n = 28) despite anti-HBs <10 mIU/mL. In 2010, 72.9% (416/571) of participants had anti-HBs ≥10 mIU/mL (67.3% in group A vs. 75.8% in group B; p 0.03). The geometric mean concentrations (GMCs) were similar in both groups. Between 2003 and 2010, anti-HBs concentrations in previously boosted individuals markedly declined with GMC dropping from 486 to 27.7 mIU/mL (p <0.001). Fifteen vaccinees showed a marked increase of antibody, possibly due to natural booster. In 2010, 96 individuals (37 of group A and 59 of group B) with anti-HBs <10 mIU/mL were boosted; all vaccinees of the former group and all but two of the latter had an anamnestic response. Post-booster GMC was higher in group B (895.6 vs. 492.2 mIU/mL; p 0.039). This finding shows that the immune memory for HBsAg persists beyond the time at which anti-HBs disappears, conferring long-term protection.     

Hepatitis B vaccination status in an at-risk adult population: long-term immunity but insufficient coverage

In France, hepatitis B (HB) vaccine has been offered to all infants since 1994, and was proposed to all children aged 11 years from 1994 to 1998. Nevertheless, HB vaccine hesitancy may result in low vaccination coverage in present-day at-risk adults. We aimed to determine HB vaccination coverage in adults attending a free testing center for sexually transmitted infections (STI). As part of routine care, three classes of data were anonymously collected from attendees over a 3-month period: results of HB serologic tests; date and number of past anti-hepatitis B virus (HBV) immunization(s) (if any) according to health records; and the risk of STI and blood-transmitted infections (BTI). The study included 735 participants (age 27.9?±?9.2; 59.9% men). According to available health records (341 participants), 56.6% had received at least three and 67.2% at least one vaccine injection(s); 57.7% had received their last injection between 1994 and 1998, reflecting the strong vaccine policy during these years. Serologic testing (in 705 participants) showed evidence of a past or active HBV infection for 33 participants; of the remaining patients, 55.3% had anti-HBs antibody titers ≥10 IU/L. This rate was not higher in participants considered at risk for STI/BTI. Of the participants who received their last vaccine injection more than 15 years previously, 90.5% had anti-HBs antibody concentrations ≥10 and 60.3% ≥100 IU/mL. HB vaccination coverage is low in this population. Most of the vaccinated participants were immunized between 1994 and 1998, suggesting a failure of catch-up immunization of adolescents and at-risk adults. Long-term seroprotection persisted among vaccinated participants.     

Hepatitis A outbreak in an institution

In February 1996, four serologically confirmed cases of hepatitis A virus (HAV) occurred in one household. Investigation showed that the source was a family member with sub-clinical HAV who attended a Unit for Learning Disabilities. Reports of two further cases in the institution followed and control measures were instigated. Contacts were unwilling to accept human normal immunoglobulin (HNIG). Following salivary antibody and serological testing, hepatitis A vaccine was offered to the non-immune. An investigation found that sub-clinical infection was significantly associated with being less than 5 years old (RR = 6.07, p < 0.005) and being in one particular classroom (RR = 6.21, p < 0.0005). None of the staff in the institution became infected. In all, 31 cases of hepatitis A (18 clinical and 13 subclinical cases) occurred. This paper (a) describes an outbreak of hepatitis A (b) refers to the use of a salivary antibody test (assay performance to be published elsewhere) (c) identifies factors associated with the acquisition of HAV and (d) endeavours to assess the effectiveness of the vaccine to contain the outbreak.     

Hepatitis A virus in cell culture

The propagation of hepatitis A virus (HAV) is shown in a rapidly growing fetal rhesus monkey kidney cell line (Frhk-4/R). In the course of ten passages through Frhk-4/R cells the HAV, which was released in the supernatants of the cell cultures, was adapted to these cells. In the tenth passage 6 days after infection, it was possible to detect low amounts of HAV in the supernatants by radioimmunoassay (RIA). With indirect immunofluorescence 3 days after infection, a specific granular fluorescence was demonstrated in the cytoplasm of cells infected with HAV from the tenth passage. A persistent infection of Frhk-4/R cells with HAV is shown over a period of 6 months. The HAV produced in Frhk-4/R cells appeared with a main peak at a density of 1.32 g/cm³ in CsCl density gradients. In the 1.32 g/cm³ fractions, typical HAV particles are shown by electron microscopy. Furthermore the HAV produced in Frhk-4/R cells is shown to be a useful antigen for diagnostic tests.     

Antibodies against Hepatitis A and Hepatitis B Virus in Intravenous Immunoglobulin Products

The worldwide seroprevalence of hepatitis A virus (HAV) and hepatitis B virus (HBV) has changed over the last two decades, indicating a declining incidence of HAV and HBV infections. Therefore, vaccinations against HAV and HBV are recommended for unimmunized people before traveling to an endemic area. Unfortunately, primary antibody deficiency (PAD) patients can only obtain humoral immunity through intravenous immunoglobulin G (IVIG) replacement and not from vaccination because of a defect in antibody production. However, few studies have analyzed the titers of antibodies against HAV or HBV in IVIG products. In this study, the titers of anti-HAV and anti-HBs antibodies were measured in nineteen lots of IVIG products from five manufacturers from three countries (A, B from Korea; C, D from Japan; and E from the USA), and trough titers in plasma were estimated. Concentrations of anti-HAV antibody ranged from 1,888–8,927 mIU/mL and estimated trough titers exceeded the minimal protective value in all evaluated IVIG products. Concentrations of anti-HBs antibody ranged from 438–965 mIU/mL in products A and B and were 157, 123, and 1,945 mIU/mL in products C, D, and E, respectively. Estimated trough titers in products A, B, and E exceeded the minimal protective value but those in products C and D did not reach this threshold. These data demonstrated that available IVIG products generally provide sufficient antibodies against HAV and HBV to protect patients with PAD, although the trough concentrations of anti-HBs antibody in two IVIG products did not reach the minimum protective value.     

不同剂量HBIG对母婴乙型肝炎病毒抗原抗体宫内传播的影响

目的探讨不同剂量乙肝免疫球蛋白（HBIG）对乙型肝炎病毒（HBV）抗原抗体宫内传播的影响。方法将母亲乙肝表面抗原（HBsAg）阳性的婴儿作为500例观察对象,根据出生前母亲是否用HBIG分为：观察1组：产前母亲孕末期28w、32w、36w各用200IU（蓉生）HBIG 200例;观察2组：产前母亲孕末期28w、32w、36w各用400IU（蓉生）HBIG 100例;对照1组：产前母亲孕末期不用HBIG 200例。观察生后12h内新生儿静脉血乙肝五项：HBsAg、乙型肝炎表面抗体（HBsAb）、乙型肝炎e抗原（HBeAg）、乙型肝炎e抗体（HBeAb）、乙型肝炎核心抗体（HBcAb）。结果观察1组200例新生儿HBsAg阳性1例,阳性率为0.5%,HBeAg阳性3例,（其中1例HBsAg同时阳性）阳性率为1.5%。对照组HBsAg阳性2例,阳性率为1%,HBeAg阳性8例,（其中2例HBsAg同时阳性）阳性率为4%。经统计学处理（HBsAg）χ2=0.336,P=0.562;（HBeAg）,χ2=2.337,P=0.126。观察1组与对照组生后24h内HBV抗原检测比较无显著差异。观察1组、观察2组与对照组HBsAb检测比较：观察1组新生儿HBsAb阳性率1%,观察2组新生儿HBsAb阳性率2%,对照组HBsAb阳性率1%,各组HBeAb和HBcAb检测比较,结果HBeAb和HBcAb检测母婴符合率均在97%-97.5%之间。结论孕妇HBV携带者产前孕末期用HBIG 200IU隔4w连用3次的方法对阻断乙肝病毒的宫内感染效果不显著。加大HBIG的用量400IU可基本阻断HBV垂直传播胎儿。但鉴于对照组宫内感染率仅4%,加大用量不适用所有HBV携带者孕妇,尤其是HBsAg单阳性孕妇。     

A role for antibodies in tumor immunity

Recent advances have demonstrated the clinical utility of specific monoclonal antibodies that recognize tumor-associated antigens on the surface of the tumor cell in the treatment of breast cancer and B cell lymphoma in humans. In addition to these studies, an experimental tumor model, where antibodies that recognize a viral-encoded tumor-specific antigen play a major role in tumor immunity, will be discussed. Together, these studies implicate antibodies as a means of providing tumor immunity against some cancers. The necessity for designing cancer vaccines that induce antibodies with specificity for antigens on the tumor cell will be discussed.     

The function of immunoglobulin A in immunity

The vast surfaces of the gastrointestinal, respiratory, and genitourinary tracts represent major sites of potential attack by invading micro-organisms. Immunoglobulin A (IgA), as the principal antibody class in the secretions that bathe these mucosal surfaces, acts as an important first line of defence. IgA, also an important serum immunoglobulin, mediates a variety of protective functions through interaction with specific receptors and immune mediators. The importance of such protection is underlined by the fact that certain pathogens have evolved mechanisms to compromise IgA-mediated defence, providing an opportunity for more effective invasion. IgA function may also be perturbed in certain disease states, some of which are characterized by deposition of IgA in specific tissues. This review details current understanding of the roles played by IgA in both health and disease.     

Vitamin A levels and immunity in humans

In animal studies, vitamin A deficiency induces a shift from type 2 (humoral) to type 1 (cellular) cytokines; there are no similar data for humans. Control of human immunodeficiency virus (HIV) and Mycobacterium tuberculosis infections requires type 1 cytokine (cellular) immunity. These infections and vitamin A deficiency are highly prevalent in Africa. We therefore examined the interactions among serum vitamin A levels, immune parameters, HIV infection status, Mycobacterium bovis BCG vaccine scarring (as an indicator of a type 1 cytokine profile), and clinical findings for 70 hospitalized children in Malawi, Africa. Directly conjugated monoclonal antibodies and flow cytometry were used to assess cell-specific cytokine production by peripheral blood monocytes and lymphocyte subpopulations. The statistical techniques employed included nonparametric statistics and logistic regression analyses. Thirty percent of the participants had severe vitamin A deficiency (<10 microg/dl), 34% had moderate deficiency (10 to <20 microg/dl), and 36% had normal levels (> or = 20 microg/dl). Vitamin A levels were lower for HIV-positive than for HIV-negative children (median, 10 and 17 microg/dl, respectively). Vitamin A-deficient children (<20 microg/dl) were more likely than non-vitamin A-deficient children to have higher proportions of natural killer (NK) cells (median, 8.3 and 5.2%, respectively) and lower ratios of interleukin-10-producing monocytes to tumor necrosis factor alpha-producing monocytes after induction (median, 1.0 and 2.3, respectively). Vitamin A-deficient children were also more likely than non-vitamin A-deficient children to exhibit respiratory symptoms (47% versus 12%) and visible BCG vaccine scars (83% versus 48%), which are indicative of a type 1 response to vaccination. Vitamin A status did not vary with gender, age, incidence of malaria parasitemia, blood culture positivity, or rates of mortality (6% of vitamin A-deficient children died versus 20% of non-vitamin A-deficient children). Lower vitamin A levels were associated with a relative type 1 cytokine dominance and proportionately more NK cells, both of which may be somewhat beneficial to persons who are exposed to HIV, M. tuberculosis, or other type 1 pathogens.