Vaccines safety; effect of supervision or SMS on reporting rates of adverse events following immunization (AEFI) with meningitis vaccine (MenAfriVac™): A randomized controlled trial

Background

To ensure vaccines safety, given the weaknesses of the national pharmacovigilance system in Cameroon, there is a need to identify effective interventions that can contribute to improving AEFI reporting.

Objective

To assess the effect of: (i) sending weekly SMS, or (ii) weekly supervisory visits on AEFI reporting rate during a meningitis immunization campaign conducted in Cameroon in 2012 using the meningitis A conjugate vaccine (MenAfriVac™).

Methods

Health facilities that met the inclusion criteria were randomly assigned to receive: (i) a weekly standardized SMS, (ii) a weekly standardized supervisory visits or (iii) no intervention. The primary outcome was the reported AEFI incidence rate from week 5 to 8 after the immunization campaign. Poisson regression model was used to estimate the effect of interventions after adjusting for health region, type of health facility, type and position of health workers as well as the cumulative number of AEFI reported from weeks 1 to 4.

Results

A total of 348 (77.2%) of 451 health facility were included, and 116 assigned to each of three groups. The incidence rate of reported AEFI per 100 health facility per week was 20.0 (15.9–24.1) in the SMS group, 40.2 (34.4–46.0) in supervision group and 13.6 (10.1–16.9) in the control group. Supervision led to a significant increase of AEFI reporting rate compared to SMS [adjusted RR = 2.1 (1.6–2.7); p < 0.001] and control [RR = 2.8(2.1–3.7); p < 0.001)] groups. The effect of SMS led to some increase in AEFI reporting rate compared to the control group, but the difference was not statistically significant [RR = 1.4(0.8–1.6); p = 0.07)].

Conclusion

Supervision was more effective than SMS or routine surveillance in improving AEFI reporting rate. It should be part of any AEFI surveillance system. SMS could be useful in improving AEFI reporting rates but strategies need to be found to improve its effectiveness, and thus maximize its benefits.     

SMS text message reminders to improve infant vaccination coverage in Guatemala: A pilot randomized controlled trial

BackgroundPatient reminder systems are an evidence-based way to improve childhood vaccination rates but are difficult to implement in low- and middle-income countries (LMICs). Short Message Service (SMS) texts may offer a potential low-cost solution, especially in LMICs where mobile phones are becoming more ubiquitous.ObjectiveTo determine if an SMS-based vaccination reminder system aimed at improving completion of the infant primary immunization series is feasible and acceptable in Guatemala.MethodsA pilot randomized controlled trial was conducted at two public health clinics in Guatemala City. Infants aged 8–14 weeks presenting for the first dose of the primary immunization series were enrolled in March–April 2013. Participants randomized into the intervention received three SMS reminders one week before the second and third dose. A follow-up acceptability survey was administered to both groups.ResultsThe participation rate was 86.8% (321/370); 8 did not own a cell phone and 12 could not use SMS. 96.9% of intervention parents were sent at least one SMS reminder prior to visit 2 and 96.3% prior to visit 3. Both intervention and usual care participants had high rates of vaccine and visit completion, with a non-statistically significant higher percentage of children in the intervention completing both visit 2 (95.0% vs. 90.1%, p = .12) and visit 3 (84.4% vs. 80.7%, p = .69). More intervention vs. usual care parents agreed that SMS reminders would be helpful for remembering appointments (p < .0001), agreed to being interested in receiving future SMS reminders (p < .0001), and said that they would be willing to pay for future SMS reminders (p = .01).ConclusionThis proof of concept evaluation showed that a new application of SMS technology is feasible to implement in a LMIC with high user satisfaction. Larger studies with modifications in the SMS system are needed to determine effectiveness (Clinical Trial Registry NCT01663636).     

Design considerations for liposomal vaccines: influence of formulation parameters on antibody and cell-mediated immune responses to liposome associated antigens

Liposomes (phospholipid bilayer vesicles) are versatile and robust delivery systems for induction of antibody and T lymphocyte responses to associated subunit antigens. In the last 15 years, liposome vaccine technology has matured and now several vaccines containing liposome-based adjuvants have been approved for human use or have reached late stages of clinical evaluation. Given the intensifying interest in liposome-based vaccines, it is important to understand precisely how liposomes interact with the immune system and stimulate immunity. It has become clear that the physicochemical properties of liposomal vaccines - method of antigen attachment, lipid composition, bilayer fluidity, particle charge, and other properties - exert dramatic effects on the resulting immune response. Here, we present a comprehensive review of the physicochemical properties of liposomal vaccines and how they influence immune responses. A discussion of novel and emerging immunomodulators that are suitable for inclusion in liposomal vaccines is also presented. Through a comprehensive analysis of the body of liposomal vaccine literature, we enumerate a series of principles that can guide the rational design of liposomal vaccines to elicit immune responses of a desired magnitude and quality. We also identify major unanswered questions in the field, pointing the direction for future study.     

Cost-effectiveness of SMS appointment reminders in increasing vaccination uptake in Lagos,Nigeria: A multi-centered randomized controlled trial

ObjectiveIt is expected that mHealth largely contribute to increasing the coverages of key maternal and child health services. This study aims to estimate the cost-effectiveness of the SMS text reminders in clients’ return visits to the health facilities for child vaccinations (incl. vitamin A supplementations), antenatal care (ANC) and family planning (FP), in urban communities of Lagos, Nigeria.MethodsA multi-centered randomized control trial was conducted at 33 primary health centers (PHCs) in Lagos, Nigeria. All the clients having visited any of the 33 PHCs for child vaccinations, ANC and FP were randomly assigned either to intervention group or to control group.The participants in the intervention group were sent an SMS text reminder two days before their appointments. Those not having showed up on the appointment dates received an additional SMS text reminder seven days after original appointment dates as defaulter tracing. The primary outcome was whether a client made return visit to PHCs for the upcoming appointments.ResultsOf 12,779 appointments for 9,368 clients during the period of 1st April to 30th June 2019, 12,175 were included in the analysis. The return rate for child vaccinations in the intervention group was significantly higher (p < 0.001) by 4.8% − 6.0% than that in the control group, consistently across all the five different timings (on time as scheduled, and by 7 days, 14 days, 30 days, and 3 months after appointment dates). No significant difference between the two groups was detected in the increase in return rates for ANC and FP services. The incremental recurrent cost was estimated at 7.90 US Dollars per return case.ConclusionSMS text reminders led to a significant increase in the number of return visits for child vaccinations, Lagos, Nigeria, while no significant increase in return visits was confirmed for ANC and FP appointments.     

生脉散对急性肝衰竭大鼠内毒素诱导细胞因子的影响

[目的]探讨生脉散对急性肝衰竭大鼠内毒素（LPS）诱导细胞因子水平的影响。[方法]采用胁氨基半乳糖腹腔注射法制作急性肝衰竭大鼠模型。予生脉散灌胃2h及8h后,检测血清LPS与细胞因子水平。[结果]D-氨基半乳糖能明显增加大鼠血清白细胞介素6（IL-6）、细胞间黏附分子1（ICAM-1）和IL-1β水平（P〈0．01）,随着D-氨基半乳糖作用时间延长的趋势明显减弱,但对血清LPS、肿瘤坏死因子α（TNF-α）水平无明显影响（P〉0．05）;生脉散能显著降低D氨基半乳糖肝衰竭大鼠血清IL-6、ICAM-1和IL-1β水平（P〈0．01,〈O．05）。LPS攻击2h和8h后,能明显诱导D-氨基半乳糖大鼠血清LPS、TNF-α、IL-6、ICAM-1和IL-1β水平增加（P〈0．01）;除在8h对TNF-α无影响外,生脉散能明显减轻LPS攻击D-氨基半乳糖大鼠后对血清LPS、TNF-α、IL-6、ICAM-1和IL-1β水平的影响（P〈0．01,〈O．05）。[结论]SD大鼠在急性肝衰竭状态下,存在严重LPS血症,并引起细胞因子水平变化的炎症级联反应,生脉散可通过调节细胞及炎症因子水平起到治疗作用。     

利用细胞培养基或动物血浆中的荧光标记产物测定鞘磷脂合酶活性

鞘磷脂合酶（SMS）催化神经酰胺（ceramide,Cer．）转变为鞘磷脂（sphingomyelin,SM）。近来的研究表明神经酰胺和鞘磷脂参与了代谢综合征的过程,因而鞘磷脂合酶被认为是开发抗代谢综合征药物的潜在靶点。鞘磷脂合酶有两个同工酶,分别称为鞘磷脂合酶1（SMS1）和鞘磷脂合酶2（SMS2）。这两种同工酶的亚细胞定位不同,在不同组织中的表达水平也有差异。到目前为止,已发表有多种方法测定组织和细胞匀浆中的总SMS活性,这些方法通过分析总反应体系或细胞内的酶促反应产物来衡量SMS活性。本文介绍一种测定SMS活性或筛选SMS抑制剂的新方法。我们将荧光标记的神经酰胺（NBD-Cer．）作为底物与细胞孵育,或者将该底物注射到小鼠体内,然后监测在细胞培养基或小鼠血浆中出现的荧光标记的鞘磷脂（NBD-SM）的含量。采用这种办法可有效检测出D609（一种鞘磷脂合酶抑制剂）对细胞和小鼠整体SMs活性的抑制作用。我们进一步采用该方法检测了SMS1基因敲除小鼠和sMs2基因敲除小鼠的SMS活性,结果发现注射底物后,SMS2基因敲除小鼠（而不是SMS1基因敲除小鼠）血浆中NBD-SM的堆积被明显阻断。因而该方法可用于检测生理或药理条件下在体或离体组织的SMS活性、筛选SMS抑制剂、甚至筛选SMS2特异性抑制剂。     

Patient acceptability of receiving short message services from an HIV patient-centered medical home

Patient-centered medical homes (PCMH) are a key component in addressing the comprehensive physical and psychosocial needs of persons living with HIV. The AIDS Resource Center of Wisconsin (ARCW) is a PCMH that has become a nationally recognized leader in addressing barriers to HIV retention in care. Recently, ARCW has become interested in the use of short message services (SMS), as SMS have been found to have positive impacts on treatment adherence, CD4⁺ counts, viral load, and appointment attendance. The purpose of this research was to evaluate patient acceptability of receiving SMS from an HIV specific PCMH, in addition to evaluating patient privacy concerns and practical details of incorporating SMS into clinical care. These constructs were evaluated through a survey of 180 ARCW patients recruited from several ARCW waiting rooms. Patients were most interested in receiving SMS from medical, dental, and pharmacy services and message content regarding appointment and medication refill reminders. Participants did not indicate the presence of significant privacy concerns and were divided nearly in half over whether ARCW should refer to itself as “ARCW” or “Your medical/dental clinic.” Prior to implementation of SMS at ARCW, further evaluation into the optimization of language into concise and easy to understand messages that maximize confidentiality and minimize patient anxiety is needed.     

Simultaneous multi‐slice (SMS) acquisition enhances the sensitivity of hemodynamic mapping using gas challenges

Hemodynamic mapping using gas inhalation has received increasing interest in recent years. Cerebrovascular reactivity (CVR), which reflects the ability of the brain vasculature to dilate in response to a vasoactive stimulus, can be measured by CO₂ inhalation with continuous acquisition of blood oxygen level‐dependent (BOLD) magnetic resonance images. Cerebral blood volume (CBV) can be measured by O₂ inhalation. These hemodynamic mapping methods are appealing because of their absence of gadolinium contrast agent, their ability to assess both baseline perfusion and vascular reserve, and their utility in calibrating the functional magnetic resonance imaging (fMRI) signal. However, like other functional and physiological indices, a major drawback of these measurements is their poor sensitivity and reliability. Simultaneous multi‐slice echo planar imaging (SMS EPI) is a fast imaging technology that allows the excitation and acquisition of multiple two‐dimensional slices simultaneously, and has been shown to enhance the sensitivity of several MRI applications. To our knowledge, the benefit of SMS in gas inhalation imaging has not been investigated. In this work, we compared the sensitivity of CO₂ and O₂ inhalation data collected using SMS factor 2 (SMS2) and SMS factor 3 (SMS3) with those collected using conventional EPI (SMS1). We showed that the sensitivity of SMS scans was significantly (p = 0.01) higher than that of conventional EPI, although no difference was found between SMS2 and SMS3 (p = 0.3). On a voxel‐wise level, approximately 20–30% of voxels in the brain showed a significant enhancement in sensitivity when using SMS compared with conventional EPI, with other voxels showing an increase, but not reaching statistical significance. When using SMS, the scan duration can be reduced by half, whilst maintaining the sensitivity of conventional EPI. The availability of a sensitive acquisition technique can further enhance the potential of gas inhalation MRI in clinical applications.