Direct and Indirect Causal Effects via Potential Outcomes*

Abstract. The use of the concept of ‘direct’ versus ‘indirect’ causal effects is common, not only in statistics but also in many areas of social and economic sciences. The related terms of ‘biomarkers’ and ‘surrogates’ are common in pharmacological and biomedical sciences. Sometimes this concept is represented by graphical displays of various kinds. The view here is that there is a great deal of imprecise discussion surrounding this topic and, moreover, that the most straightforward way to clarify the situation is by using potential outcomes to define causal effects. In particular, I suggest that the use of principal stratification is key to understanding the meaning of direct and indirect causal effects. A current study of anthrax vaccine will be used to illustrate ideas.     

A modified false discovery rate multiple-comparisons procedure for discrete data, applied to human immunodeficiency virus genetics

Summary.  To help to design vaccines for acquired immune deficiency syndrome that protect broadly against many genetic variants of the human immunodeficiency virus, the mutation rates at 118 positions in HIV amino-acid sequences of subtype C versus those of subtype B were compared. The false discovery rate (FDR) multiple-comparisons procedure can be used to determine statistical significance. When the test statistics have discrete distributions, the FDR procedure can be made more powerful by a simple modification. The paper develops a modified FDR procedure for discrete data and applies it to the human immunodeficiency virus data. The new procedure detects 15 positions with significantly different mutation rates compared with 11 that are detected by the original FDR method. Simulations delineate conditions under which the modified FDR procedure confers large gains in power over the original technique. In general FDR adjustment methods can be improved for discrete data by incorporating the modification proposed.     

Evaluation of Proactive and Reactive Strategies for Polio Eradication Activities in Pakistan and Afghanistan

Only Pakistan and Afghanistan reported any polio cases caused by serotype 1 wild polioviruses (WPV1s) in 2017. With the dwindling cases in both countries and pressure to finish eradication with the least possible resources, a danger exists of inappropriate prioritization of efforts between the two countries and insufficient investment in the two countries to finish the job. We used an existing differential‐equation‐based poliovirus transmission and oral poliovirus (OPV) evolution model to simulate a proactive strategy to stop transmission, and different hypothetical reactive strategies that adapt the quality of supplemental immunization activities (SIAs) in response to observed polio cases in Pakistan and Afghanistan. To account for the delay in perception and adaptation, we related the coverage of the SIAs in high‐risk, undervaccinated subpopulations to the perceived (i.e., smoothed) polio incidence. Continuation of the current frequency and quality of SIAs remains insufficient to eradicate WPV1 in Pakistan and Afghanistan. Proactive strategies that significantly improve and sustain SIA quality lead to WPV1 eradication and the prevention of circulating vaccine‐derived poliovirus (cVDPV) outbreaks. Reactive vaccination efforts that adapt moderately quickly and independently to changes in polio incidence in each country may succeed in WPV1 interruption after several cycles of outbreaks, or may interrupt WPV1 transmission in one country but subsequently import WPV1 from the other country or enable the emergence of cVDPV outbreaks. Reactive vaccination efforts that adapt independently and either more rapidly or more slowly to changes in polio incidence in each country may similarly fail to interrupt WPV1 transmission and result in oscillations of the incidence. Reactive strategies that divert resources to the country of highest priority may lead to alternating large outbreaks. Achieving WPV1 eradication and subsequent successful OPV cessation in Pakistan and Afghanistan requires proactive and sustained efforts to improve vaccination intensity in under‐vaccinated subpopulations while maintaining high population immunity elsewhere.     

Student and faculty perceptions about mandatory influenza vaccinations on a health sciences campus

Objective: To examine the perceptions among faculty and health professional students regarding mandatory vaccination policies on a health sciences campus. Participants: A total of 296 faculty and 244 students completed surveys during Fall 2015. Methods: The online survey administered to individuals who received the influenza vaccine during the fall 2015 influenza vaccination clinic season included five items evaluating perceptions of employer mandatory vaccination requirements. Results: Chi-square analysis indicated that although faculty and students agree mandatory vaccinations in a health care environment are appropriate, faculty are more likely than students to get vaccinated in the absence of a mandate. Additionally, a small fraction of faculty would consider employment elsewhere when facing this mandate. Conclusions: Overall, faculty and students had favorable perceptions about mandatory influenza vaccine policies. Since students were less likely to be vaccinated in the absence of a mandate, education of students should be improved to support the importance of vaccinations in a health care environment.     

Meningococcal serogroup B outbreak response University of Wisconsin-Madison

A meningococcal serogroup B (MenB) outbreak at a large public university prompted an emergency response to immunize undergraduates. Objective: To report on a successful meningococcal serogroup B (MenB) vaccine clinic response at a large public university. Methods: We assembled the team leaders to write this case report. Results: Activation of the emergency plan and points of dispensing required cooperation of many units on campus under the leadership of university health officials with support from Centers for Disease Control and Prevention, state division of public health and the city-county health department. Significant efforts to provide consistent messages to students and parents regarding the outbreak and the availability of the MenB vaccines were made. Volunteers were recruited to staff the clinics alongside university healthcare providers. Over 22,000 doses of vaccine were administered. Conclusion: We report our experience and lessons learned which may be helpful to universities in preventing and responding to disease outbreaks.     

Gauging the Acceptability of HIV Vaccines: An Exploratory Study Examining Knowledge,Attitudes, and Beliefs Among Injecting Drug Users in Viet Nam

ABSTRACT

In contrast to other countries in Southeast Asia, the HIV/ AIDS epidemic is in the initial stages in Viet Nam, although the rates have increased notably since 1997. This study examined attitudes towards the use of an HIV vaccine (when one becomes available) as a means for preventing the disease. Since injecting drug users are the great majority of those affected by the HIV/AIDS epidemic in Viet Nam, two focus groups (n = 18) were conducted among this population to identify potential barriers and incentives for HIV vaccination. Most were willing to be vaccinated if an HIV vaccine were available. Although there were some concerns about side effects, financial costs, and stigmatization, the benefits were seen to outweigh the risks. The findings may help governments better understand the potential demand for this type of vaccine and design social marketing campaigns for post-trial HIV vaccine dissemination in order to maximize potential uptake of an HIV vaccine.     

复合免疫刺激物——大肠杆菌苗的研制及效力测定

采用对比试验方法 ,以小白鼠为实验动物 ,进行了复合免疫刺激物———大肠杆菌苗的研制及效力测定。结果表明 :试验组菌苗的保护率为 84 .6 2 % ,高于对照组、氢氧化铝胶苗组 5 3.85 %(P <0 .0 5 )、蜂胶佐剂苗组 5 8.33% (P <0 .0 5 )、空白对照组 38.4 6 % (P <0 .0 1) ;试验组小白鼠的增重率为 2 7.5 2 % ,高于对照组氢氧化铝胶苗组 2 2 .31% (P <0 .0 1)、蜂胶佐剂苗组 2 3.98% (P <0 .0 1)、空白对照组 17.2 2 % (P <0 .0 1) ;试验组免疫器官指数为 8.0 1% ,高于空白对照组 7.6 7% (P <0 .0 1)与铝胶苗组 7.96 % (P >0 .0 5 )。表明该复合免疫刺激物———大肠杆菌苗的免疫效力较好 ,复合免疫刺激物具有较强的免疫增强力 ,是一种较好的免疫佐剂。     

The Special Historical Section of the Journal of American College Health

Abstract

Objective: To identify human papillomavirus (HPV) infection and HPV vaccine–related attitudes among college-aged women and the relationship between HPV vaccine uptake and subsequent sexual behaviors. Methods: PubMed, MEDLINE, CINAHL, and Google Scholar searches were performed from 2006, the date after the first HPV vaccine became available, to present. Results: Of the 13 studies identified, most were cross-sectional. College-aged women saw HPV infection as serious and had positive attitudes toward the HPV vaccine. Barriers (ie, cost, lack of insurance coverage) existed that prevented women from obtaining the vaccine and many women did not see themselves at risk for HPV. The vaccine uptake rate, although increasing, has been slow. Conclusion: College-aged women in the United States may need unbiased information about HPV and HPV vaccine. Studies that focus on risk perception and the relationship between knowledge, attitudes, vaccine uptake, and sexual behaviors are needed to inform interventions and public health programs.     

The Costs of Future Polio Risk Management Policies

Decisionmakers need information about the anticipated future costs of maintaining polio eradication as a function of the policy options under consideration. Given the large portfolio of options, we reviewed and synthesized the existing cost data relevant to current policies to provide context for future policies. We model the expected future costs of different strategies for continued vaccination, surveillance, and other costs that require significant potential resource commitments. We estimate the costs of different potential policy portfolios for low-, middle-, and high-income countries to demonstrate the variability in these costs. We estimate that a global transition from routine immunization with oral poliovirus vaccine (OPV) to inactivated poliovirus vaccine (IPV) would increase the costs of managing polio globally, although routine IPV use remains less costly than routine OPV use with supplemental immunization activities. The costs of surveillance and a stockpile, while small compared to routine vaccination costs, represent important expenditures to ensure adequate response to potential outbreaks. The uncertainty and sensitivity analyses highlight important uncertainty in the aggregated costs and demonstrates that the discount rate and uncertainty in price and administration cost of IPV drives the expected incremental cost of routine IPV vs. OPV immunization.