Influenza vaccination for HIV-positive people: Systematic review and network meta-analysis

BackgroundPeople with Human Immunodeficiency Virus (HIV) are highly susceptible to influenza-related morbidity and mortality. In order to assess comparative efficacy of influenza vaccine strategies among HIV-positive people, we performed a systematic review and Bayesian network meta-analysis (NMA).MethodsIn this systematic review, we searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL between 1946 and July 2015 for randomized controlled trials (RCTs) on influenza vaccines for HIV-positive adults reporting seroconversion or seroprotection outcomes. The NMAs were conducted within a Bayesian framework and logistic models were used for comparing the effect of the vaccine strategies on the two outcomes.ResultsA total of 1957 publications were identified, 143 were selected for full review, and 13 RCTs were included in our final analysis. Fourteen separate NMAs were conducted by outcomes, vaccine strain, and different outcome measurement timepoints. For example, compared with the 15 μg single vaccine strategy, the odds ratio was the highest for the adjuvant 7.5 μg booster strategy (2.99 [95% credible interval 1.18–7.66]) when comparing seroconversion for H1N1 at 14–41 days after the last dose of vaccination and for the 60 μg single strategy (2.33 [1.31–4.18]) when comparing seroconversion for strain B.ConclusionsThe adjuvant 7.5 μg booster and 60 μg single vaccine strategies provided better seroconversion and seroprotection outcomes. These findings have important implications for national and international guidelines for influenza vaccination for HIV-positive people and future research.     

Reduced serologic sensitivity to influenza A virus illness among inactivated influenza vaccinees

We compared ≥4-fold increases in antibody titers by hemagglutination inhibition assay to RT-PCR results among 42 adults with PCR-confirmed influenza A virus illnesses. Serologic sensitivity was higher among unvaccinated (69%, 95% confidence interval [CI] = 48–90%) than vaccinated healthcare personnel (38%, 95% CI = 29–46%) in a 2010–11 prospective cohort.     

金华市MSM队列HIV阳转及高危行为变化情况

目的了解金华市男男性行为人群（MSM）的艾滋病病毒（HIV）抗体阳转及高危行为变化情况。方法采用前瞻性队列研究,招募符合纳入标准的MSM组建队列。纳入队列的MSM每隔3个月进行一次随访调查,并采集血样检测HIV抗体。结果共纳入90名HIV抗体阴性的MSM,队列基线调查艾滋病防治核心知识知晓率为83.3%,队列保持率为78.9%（71/90）,比较基线调查和随访到的性行为情况,随着随访次数增加,最近3个月与同性性伴发生安全性行为所占构成比增加;最近3个月与固定同性性伴和临时同性性伴发生性行为时都采取保护措施的比例有明显提高,与异性性伴发生性行为时安全套使用情况无变化。HIV血清抗体阳转率为3.9/100人年。结论参与队列定期随访和检测后,MSM的高危性行为有所下降。由MSM社会组织鼓励动员参加定期随访和检测是值得推广的有效干预措施。     

Immune response to hepatitis B vaccination in drug using populations: A systematic review and meta-regression analysis

Injecting and non-injecting drug users are at increased risk of contracting HBV infection, and show lower antibody response to hepatitis B vaccination compared to the general population. This systematic review and meta-regression analysis aimed to estimate seroprotection rates and identify host or vaccine factors associated with varying immune response following hepatitis B vaccination in drug using populations. Original research articles were searched using online databases (Medline, PubMed, and Embase) and from reference lists of eligible articles. HBV vaccine intervention studies reporting seroprotection rates in drug users, published in English during or after 1989 were eligible. Of 978 citations reviewed, 11 studies were eligible and included for final analysis. The reported seroprotection rates ranged from 54.5% to 97.1%. The studies were significantly heterogeneous (Q = 180.850, p = 0.000). Measurement of anti-HBs antibody at 2 months after the third vaccine dose (RR = 2.62, 95%CI = 1.16–5.94, p = 0.026) was significantly associated with higher seroprotection rates compared to measurement at 1 month and 6 month following third vaccine dose. Age, gender, current drug use, vaccine dose and schedule, anti-HBc, anti-HCV and anti-HIV antibody seropositivity, and proportion of IDU study population did not show a significant association with seroprotection rates. Recommendations for future research include the definition of a standardized time point for the measurement of anti-HBs antibody levels, to enhance comparability of the immune response between different studies. Studies should strive to accurately report all potentially relevant factors affecting immune response to vaccine. Long-term follow up studies are needed to assess the seroprotection status in drug using populations receiving hepatitis B vaccine by standard or accelerated schedules.     

Risk for the occupational infection by cytomegalovirus among health-care workers

BackgroundCytomegalovirus (CMV) are ubiquitously distributed worldwide, causing a wide range of clinical manifestations from congenital infection to a life-threatening disease in immunocompromised individuals. CMV can be transmitted via human-to-human contact through body fluids; however, the risk of CMV infection among healthcare workers (HCWs) has not been fully evaluated.AimThis study aimed to assess the risk of CMV infection among HCWs through daily medical practices.MethodsSerum samples from HCWs at Osaka University Hospital (Japan) were analysed. Initially, we compared CMV IgG seropositivity among HCWs (medical doctors, nurses, and others) in 2017, which was examined after 1 year to evaluate seroconversion rates among those with seronegative results. Then, we examined CMV seroconversion rates in HCWs who were exposed to blood and body fluids.FindingsWe analysed 1153 samples of HCWs (386 medical doctors, 468 nurses, and 299 others), of which CMV seropositivity rates were not significantly different (68.9%, 70.3%, and 70.9%, respectively). Of these, 63.9% (221/346) of CMV seronegative HCWs were followed after 1 year, with CMV seroconversion rates of 3.2% (7/221). Among 72 HCWs who tested negative for CMV IgG when exposed to blood and body fluids, the CMV seroconversion rate was 2.8% (2/72). The CMV seroconversion rates between the two situations were not significantly different.ConclusionOur study indicated that CMV infection through daily patient care seems quite rare. Further well-designed studies with a large sample size are warranted to verify our finding.     

上海市慢性乙型肝炎自然史的回顾性队列研究

目的 研究上海市慢性乙型肝炎病人的慢性乙型肝炎自然史。方法 以回顾性队列研究的方式,比较1981－1993年确诊的322例慢性乙型肝炎有肝硬化者和无肝硬化者的失代偿性肝硬化发生率、肝癌发生率、生存率以及两组对象死于肝癌、肝脏疾病和全死因的标化死亡率比（SMR）。结果 无肝硬化组和有肝硬化组的人年病死率分别为7．6‰和35．2‰,肝癌人年发生率依次为2．8‰和8．2‰,失代偿性肝硬化人年发生率分别为6．7‰和35．6‰。SMR分析两组对象全死亡率、肝癌和肝脏疾病病死率均高于上海市一般人群,尤以有肝硬化组为甚。结论 上述队列中有肝硬化组的生存率、不发生失代偿性肝硬化率显著低于无肝硬化组,两组慢性乙型肝炎患者死于肝癌、肝脏疾病和总死亡的SMR显著高于上海市一般人群。     

Shortening of the diagnostic window with a new combined HIV p24 antigen and anti-HIV-1/2/O screening test

Because antibodies to the human immunodeficiency virus (HIV) are absent in the very early phase of HIV infection, there remains a slight residual risk for HIV transmission by blood donations by viremic but antibody negative donations. To shorten the diagnostic window between infection and the detection of antibodies, Enzygnost® HIV Integral (Dade Behring, Germany) was developed. With this new test, HIV p24 antigen and HIV antibodies can be detected simultaneously in a single test. In a multicenter study the new screening assay has been compared with various tests that detect only HIV antibodies or HIV p24 antigen and with assays which permit a simultaneous detection of HIV antigen and HIV antibodies. The new assay showed 100% sensitivity for the detection of antibodies to HIV-1, groups M (n=1102) and O (n=55), and HIV-2 (n=289). In 23 out of 52 seroconversion panels, seroconversion was detected 2–18 days earlier with the new combined antigen/antibody test compared to single antibody tests. All samples from a viral load panel (n=451), all samples containing p24 antigen (n=302), and all but one of the cell culture supernatants (n=38) infected with various HIV-1 subtypes or HIV-2 were identified reliably by the new test. The specificity of the assay for 4002 unselected blood donors was 99.78% initially and 99.80% after retesting. Potentially interfering factors had no systematic influence on specificity. By testing for p24 antigen, which is present prior to the onset of antibody production in some cases of recent HIV infection, the new assay reduces the diagnostic window as compared to third generation screening assays, thus permitting an earlier diagnosis of HIV infection.     

Plant-produced Bluetongue chimaeric VLP vaccine candidates elicit serotype-specific immunity in sheep

Bluetongue (BT) is a hemorrhagic non-contagious, biting midge-transmitted disease of wild and domestic ruminants that is caused by bluetongue virus (BTV). Annual vaccination plays a pivotal role in BT disease control in endemic regions. Due to safety concerns of the current BTV multivalent live attenuated vaccine (LAV), a safe efficacious new generation subunit vaccine such as a plant-produced BT virus-like particle (VLP) vaccine is imperative. Previously, homogenous BTV serotype 8 (BTV-8) VLPs were successfully produced in Nicotiana benthamiana plants and provided protective immunity in sheep. In this study, combinations of BTV capsid proteins from more than one serotype were expressed and assembled to form chimaeric BTV-3 and BTV-4 VLPs in N. benthamiana plants. The assembled homogenous BTV-8, as well as chimaeric BTV-3 and chimaeric BTV-4 VLP serotypes, were confirmed by SDS-PAGE, Transmission Electron microscopy (TEM) and protein confirmation using liquid chromatography-mass spectrometry (LC-MS/MS) based peptide sequencing. As VP2 is the major determinant eliciting protective immunity, the percentage coverage and number of unique VP2 peptides detected in assembled chimaeric BT VLPs were used as a guide to assemble the most appropriate chimaeric combinations. Both plant-produced chimaeric BTV-3 and BTV-4 VLPs were able to induce long-lasting serotype-specific neutralizing antibodies equivalent to the monovalent LAV controls. Antibody levels remained high to the end of the trial. Combinations of homogenous and chimaeric BT VLPs have great potential as a safe, effective multivalent vaccine with the ability to distinguish between vaccinated and infected individuals (DIVA) due to the absence of non-structural proteins.     

Entecavir as treatment for reactivation of hepatitis B in immunosuppressed patients

AIM: To study the efficacy and safety of entecavir (ETV) as first-line therapy for hepatitis B virus (HBV) reactivation due to immunosuppression. METHODS: Four patients that were treated with different immunosuppressive regimens for hematological malignancies, who presented with HBV reactivation were treated with ETV. Clinical outcome, biochemical and virological factors, including quantitative hepatitis B surface antigen (HBsAg) were studied. RESULTS: In all patients, ETV induced suppression of HBV, and rapid clinical improvement without side effects. In one patient with an alanine aminotransferase (ALT) flare, tenofovir was added after 3 mo of treatment. Until death from disease progression at 6 mo after treatment initiation, this patient did not clear HBV infection. Retrospectively, it is highly probable that thepatient had been non-adherent. In the other three patients, the virological responses were associated with an expeditious decrease in quantitative HBsAg titers with negativity after 2 mo, and all three had HBsAg seroconversion. In one patient, HBV DNA reached a plateau after 3 mo, before becoming undetectable after 1 year, despite early ALT normalization and undetectable quantitative HBsAg. CONCLUSION: ETV seems to be effective and safe treatment for HBV reactivation. Monitoring of quantitative HBsAg might be an additional useful tool to monitor treatment response.     

提高HBeAg阳性慢性乙型肝炎患者持久免疫控制的治疗策略

HBeAg阳性和阴性慢性乙型肝炎(CHB)是慢性HBV感染的两种临床表现类型.相对于HBeAg阴性CHB,HBeAg阳性CHB患者具有相对年轻、病程短、炎症活动明显(转氨酶水平高)、病毒复制活跃等特点,所以对HBeAg阳性CHB患者不仅需要进行积极的抗病毒治疗,而且如获得免疫控制则具有明确的临床治疗终点,远期预后会明显改善,因此更能体现治疗价值.故本文仅针对HBeAg阳性CHB患者,探讨如何提高持久免疫控制的相关问题.