Immunogenicity of the hepatitis A vaccine 20 years after infant immunization

To determine the duration of immunity provided by the Hepatitis A vaccination (HepA), we evaluated a cohort of participants in Alaska 20 years after being immunized as infants. At recruitment, participants received two doses of inactivated HepA vaccine on one of three schedules. We conducted hepatitis A antibody (anti-HAV) testing for participants at the 20-year time-point. Seventy-five of the original 183 participants (41%) were available for follow-up. The overall anti-HAV geometric mean concentration was 29.9 mIU/mL (95% CI 22.4 mIU/mL, 39.7 mIU/mL) and 50 participants (68%) remained seropositive (titer ≥ 20 mIU/mL). Using a fractional polynomial model, the predicted percent seropositive at 25 years was 55.3%, 49.8% at 30 years and 45.7% at 35 years, suggesting that the percent sero-positive could drop below 50% earlier than previously expected. Further research is necessary to understand if protection continues after seropositivity diminishes or if a HepA booster dose may become necessary.     

Invasive pneumococcal disease in children under 16 years of age: Incomplete rebound in incidence after the maximum effect of PCV13 in 2012/13 in Germany

ObjectiveTo identify a potential nadir of the impact of pneumococcal conjugate vaccination (PCV) in infancy on invasive pneumococcal diseases (IPD) in children under 16 in Germany.MethodsActive surveillance on IPD based on two independent data sources with capture-recapture correction for underreporting. Annual incidence rates by age group, serotypes, site of infection, and relative incidence reduction compared to pre-vaccination period (1997–2001) at nadir and for the most recent season are reported. We calculated vaccine coverage at the age of 24 months using health insurance claims data.Results96–97% of children had received at least two doses of PCV since 2009. The maximum impact on overall IPD incidence was achieved in 2012/13 (−48% [95% CI: −55%; −39%]) with a rebound to −26% [95% CI: −36%; −16%] in 2015/16. Non-PCV13 serotypes accounted for 84.1% of the IPD cases in 2015/16. The most frequent non-PCV serotypes in IPD in 2014/15 and 2015/16 were 10A, 24F, 15C, 12F, 38, 22F, 23B, and 15B. The impact at nadir was highest in children 0–1 years of age both in meningitis and non-meningitis cases, whereas the impact for other age groups was higher for meningitis cases. The rebound mainly pertained to non-meningitis cases.ConclusionThe maximum impact of pneumococcal conjugate vaccination has been attained and signs of a rebound are apparent. Sustained surveillance for IPD in children is warranted to assess whether these trends will continue. There may be a need for vaccines using antigens common to all serotypes.     

Pharmacokinetics of 4′-cyano-2′-deoxyguanosine,a novel nucleoside analog inhibitor of the resistant hepatitis B virus,in a rat model of chronic kidney disease

IntroductionThe novel nucleoside analog, 4′-cyano-2′-deoxyguanosine (CdG), possesses inhibitory activity against both the wild-type and resistant hepatitis B virus. Since the dosage of the currently available nucleoside analog preparations needs to be adjusted, depending on renal function, we investigated the effect of renal dysfunction on the pharmacokinetics of CdG in a rat model of chronic kidney disease (CKD).MethodsCKD model rats were either intravenously or orally administered CdG at a dose of 1 mg/kg. The concentration of CdG in plasma, organs (liver and kidney) and urine samples were determined by means of a UPLC system interfaced with a TOF-MS system.ResultsFollowing intravenous administration, the plasma retention of CdG was prolonged in CKD model rats compared to healthy rats. In addition, the clearance of CdG was well correlated with plasma creatinine levels in CKD model rats. Similar to the results for intravenous administration, the plasma concentration profiles of CdG after oral administration were also found to be much higher in CKD model rats than in healthy rats. However, the results for the organ distribution and urinary excretion of CdG, the profiles of which were similar to that of healthy rats, indicated that CdG did not accumulate to a significant extent in the body.ConclusionThe extent of renal dysfunction has a direct influence on the pharmacokinetics (plasma retention) of CdG without a significant accumulation, indicating that the dosage of CdG will be dependent on the extent of renal function. .     

Intraocular penetration of liposomal amphotericin B after intravenous injection in inflamed human eyes

PurposeTo determine the intraocular penetration of amphotericin B (AMPH-B) after an intravenously injection of liposomal amphotericin B (L-AMB) in inflamed human eyes.MethodsSeven eyes of 5 patients with fungal eye diseases (endophthalmitis in 6 eyes and keratitis in 1 eye) were treated with intravenous injections of 100–250 mg/day of L-AMB. Samples of blood, corneal button, aqueous humor, and vitreous humor were collected and assessed for AMPH-B.ResultsThe AMPH-B level in the cornea (604.0 μg/g) of the case with fungal keratitis exceeded the minimum inhibitory concentration. However, the levels in the aqueous and vitreous humors of the cases with fungal endophthalmitis were lower, e.g., 0.02 ± 0.01 μg/ml (0.09% of serum level) in the aqueous humor and 0.05 ± 0.08 μg/ml (0.17% of serum level) in the vitreous humor.ConclusionsThe AMPH-B levels administered intravenously were very low in the aqueous and vitreous humors. Our findings indicate that intravenous L-AMB can be considered only for patients with mild endogenous fungal endophthalmitis, e.g., isolated chorioretinitis without vitreous extensions.     

青年男男性行为人群艾滋病、梅毒感染的流行病学调查

目的 掌握南京地区近5年青年男男性行为人群（young men who have sex with men,YMSM）艾滋病和梅毒感染率,分析YMSM感染人类免疫缺陷病毒（human immunodeficiency virus,HIV）危险因素。方法 利用2013-2017年南京市MSM人群横断面调查研究,筛选其中16~24周岁YMSM调查资料进行分析。结果 纳入调查的YMSM共1 029名。以未婚、汉族和自我认同为同性恋为主,文化程度大专及以上占73.66%。HIV、现症梅毒和既往梅毒总感染率分别为8.65%、4.18%和8.84%,5年间变化趋势均无统计学意义（均有P>0.05）。YMSM通过网络寻找性伴的比例从63.96%上升至73.86%;最近半年发生无保护性肛交（unprotected anal intercourse,UAI）比例从55.86%下降至36.93%,最近一次肛交安全套使用比例从62.00%上升至80.71%,差异均有统计学意义（均有P<0.05）。多因素Logistic回归分析显示,最近半年发生过UAI、YMSM性角色为被插入方和双重角色、现症梅毒感染是YMSM感染HIV的危险因素。结论 南京市YMSM人群HIV和梅毒感染率均处于较高水平,大部分YMSM接受过高等教育,今后应长期持续学校艾滋病性病预防控制综合措施的落实。应积极开发针对YMSM的网络干预措施和方法。坚持使用安全套和及时规范诊疗性病是降低YMSM人群感染HIV的关键措施。     

Workshop report: Nucleic acid delivery devices for HIV vaccines: Workshop proceedings,National Institute of Allergy and Infectious Diseases,Bethesda, Maryland,USA, May 21, 2015

On May 21st, 2015, the U.S. National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on delivery devices for nucleic acid (NA) as vaccines in order to review the landscape of past and future technologies for administering NA (e.g., DNA, RNA, etc.) as antigen into target tissues of animal models and humans. Its focus was on current and future applications for preventing and treating human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) disease, among other infectious-disease priorities. Meeting participants presented the results and experience of representative clinical trials of NA vaccines using a variety of alternative delivery devices, as well as a broader group of methods studied in animal models and at bench top, to improve upon the performance and/or avoid the drawbacks of conventional needle-syringe (N–S) delivery. The subjects described and discussed included (1) delivery targeted into oral, cutaneous/intradermal, nasal, upper and lower respiratory, and intramuscular tissues; (2) devices and techniques for jet injection, solid, hollow, and dissolving microneedles, patches for topical passive diffusion or iontophoresis, electroporation, thermal microporation, nasal sprayers, aerosol upper-respiratory and pulmonary inhalation, stratum-corneum ablation by ultrasound, chemicals, and mechanical abrasion, and kinetic/ballistic delivery; (3) antigens, adjuvants, and carriers such as DNA, messenger RNA, synthesized plasmids, chemokines, wet and dry aerosols, and pollen-grain and microparticle vectors; and (4) the clinical experience and humoral, cellular, and cytokine immune responses observed for many of these target tissues, technologies, constructs, and carriers. This report summarizes the presentations and discussions from the workshop (https://web.archive.org/web/20160228112310/https://www.blsmeetings.net/NucleicAcidDeliveryDevices/), which was webcast live in its entirety and archived online (http://videocast.nih.gov/summary.asp?live=16059).     

Measuring vaccine acceptance among Canadian parents: A survey of the Canadian Immunization Research Network

Parental decision making about childhood vaccinations is complex and multidimensional. There is a perception that the number of parents having concerns regarding childhood vaccinations has been increasing in Canada. The aim of this study was to explore vaccine hesitancy among Canadian parents and to examine factors associated with a parent’s intention to vaccinate his/her child. Informed by the Theory of Planned Behaviour (TPB) this study assesses potential associations between parents’ knowledge, attitudes and beliefs toward vaccination and their intention to vaccinate their child in the future. A national sample of Canadian parents of children aged 24–59 months (N = 2013) was surveyed using an online survey methodology. Half of the surveyed parents strongly intended to have their child vaccinated in the future. Parents’ information needs and searches as well as parents’ trust in different institutions were associated with intention to vaccinate. Parents who reported having frequently looked for vaccine information, who considered that it was their role as parents to question vaccines, or who had previously experienced difficulty accessing vaccination services were less likely to strongly intend to vaccinate their child in the future. Parents who had a high level of trust in doctors and public health were most likely to strongly intend to vaccinate their child. Results of the multivariate analysis showed that positive attitudes (aOR = 8.0; 95% CI: 6.0, 10.4), higher perceived social support (aOR = 3.0; 95% CI: 2.3, 3.93), and higher perceived behavioural control (aOR = 1.8; 95% CI: 1.4, 2.43) were associated with parents’ intention to vaccinate their child. Findings of this study suggest that trust-building interventions that promote pro-vaccine social norms and that address negative attitudes toward vaccination could enhance vaccine acceptance among Canadian parents.     

What has been achieved in HIV prevention,treatment and care for people who inject drugs, 2010–2012? A review of the six highest burden countries

ObjectiveIn 2010 the international HIV/AIDS community called on countries to take action to prevent HIV transmission among people who inject drugs (PWID). To set a baseline we proposed an “accountability matrix”, focusing upon six countries accounting for half of the global population of PWID: China, Malaysia, Russia, Ukraine, Vietnam and the USA. Two years on, we review progress.DesignWe searched peer-reviewed literature, conducted online searches, and contacted experts for ‘grey’ literature. We limited searches to documents published since December 2009 and used decision rules endorsed in earlier reviews.ResultsPolicy shifts are increasing coverage of key interventions for PWID in China, Malaysia, Vietnam and Ukraine. Increases in PWID receiving antiretroviral treatment (ART) and opioid substitution treatment (OST) in both Vietnam and China, and a shift in Malaysia from a punitive law enforcement approach to evidence-based treatment are promising developments. The USA and Russia have had no advances on PWID access to needle and syringe programmes (NSP), OST or ART. There have also been policy setbacks in these countries, with Russia reaffirming its stance against OST and closing down access to information on methadone, and the USA reinstituting its Congressional ban on Federal funding for NSPs.ConclusionsPrevention of HIV infection and access to HIV treatment for PWID is possible. Whether countries with concentrated epidemics among PWID will meet goals of achieving universal access and eliminating new HIV infections remains unknown. As long as law enforcement responses counter public health responses, health-seeking behaviour and health service delivery will be limited.