Friday, October 01, 2021

Assessment of Communication Strategies for Mitigating COVID-19 Vaccine-Specific Hesitancy in Canada

JAMA Netw Open. 2021;4(9):e2126635. doi:10.1001/jamanetworkopen.2021.26635

Original Investigation 
Public Health
September 30, 2021
Key Points

Question  Are there communication strategies that can reduce COVID-19 vaccine-specific hesitancy?

Findings  In a between-participants survey study of adult Canadian citizens, individuals who were provided information on the death prevention potential of less-preferred vaccines, such as AstraZeneca and Johnson & Johnson, reported more confidence in their effectiveness and a higher likelihood of taking these vaccines if offered compared with those who did not receive this information. Information on the overall effectiveness of these vaccines at preventing symptomatic COVID-19 showed the opposite result.

Meaning  These findings suggest that communication strategies that focus on the death prevention potential of less-preferred COVID-19 vaccines have the potential to improve their uptake, whereas focusing on such metrics as their comparatively less impressive overall effectiveness at preventing symptomatic COVID-19 could undermine these efforts.

Abstract

Importance  Ensuring widespread uptake of available COVID-19 vaccinations, each with different safety and efficacy profiles, is essential to combating the unfolding pandemic.

Objective  To test communication interventions that may encourage the uptake of less-preferred vaccines.

Design, Setting, and Participants  This online survey was conducted from March 24 to 30, 2021, using a nonprobability convenience sample of Canadian citizens aged 18 years or older, with quota sampling to match 2016 Canadian Census benchmarks on age, gender, region, and language. Respondents completed a 2-by-2-by-2 factorial experiment with random assignment of brand (AstraZeneca or Johnson & Johnson), information about the vaccine’s effectiveness against symptomatic infection (yes or no), and information about the vaccine’s effectiveness at preventing death from COVID-19 (yes or no) before being asked about their willingness to receive their assigned vaccine and their beliefs about its effectiveness.

Exposures  Respondents were randomly assigned a vaccine brand (AstraZeneca or Johnson & Johnson) and information about the vaccine’s effectiveness against symptomatic COVID-19 infection (yes or no) and at preventing death from COVID-19 (yes or no).

Main Outcomes and Measures  Respondents’ self-reported likelihood of taking their assigned vaccine if offered (response categories: very likely, somewhat likely, not very likely, or not at all likely, scaled 0-1) and their beliefs about their assigned vaccine’s effectiveness (response categories: very effective, somewhat effective, not very effective, or not at all effective, scaled 0-1) were measured.

Results  A total of 2556 Canadian adults responded to the survey (median [IQR] age, 50 [34-63] years; 1339 women [52%]). The self-reported likelihood of taking an assigned AstraZeneca or Johnson & Johnson vaccine was higher for respondents given information about their assigned vaccine’s effectiveness at preventing death from COVID-19 (b, 0.04; 95% CI, 0.01 to 0.06) and lower among those given information about its overall effectiveness at preventing symptomatic transmission (b, −0.03; 95% CI, −0.05 to 0.00), compared with those who were not given the information. Perceived effectiveness was also higher among those given information about their assigned vaccine’s effectiveness at preventing death from COVID-19 (b, 0.03; 95% CI, 0.01 to 0.05) and lower among those given information about their assigned vaccine’s overall efficacy at preventing symptomatic infection (b, −0.05; 95% CI, −0.08 to −0.03), compared with those who were not given this information. The interaction between these treatments was neither substantively nor statistically significant.

Conclusions and Relevance  These findings suggest that providing information on the effectiveness of less-preferred vaccines at preventing death from COVID-19 is associated with more confidence in their effectiveness and less vaccine-specific hesitancy. These results can inform public health communication strategies to reduce hesitancy toward specific COVID-19 vaccines.

Introduction

Mass vaccination campaigns are rapidly proceeding globally. These campaigns make use of vaccines with different characteristics, such as their country of origin, number of required doses, underlying technology (eg, mRNA), and their levels of efficacy and safety. Containing the COVID-19 pandemic will require vaccinating at least 70% of US individuals1 and billions more globally. It will also likely require follow-up or booster vaccinations. Understanding the sources of hesitancy and identifying correctives is, thus, vitally important for global public health.

Important research identifies sources of COVID-19 vaccine hesitancy. Resistance appears to be higher among people with low trust in expertise2 and, in the US, among Republican party identifiers.3 Vaccine hesitancy is also higher among racial and ethnic minority groups, women, those with more skepticism about childhood vaccines, and those skeptical of the severity of the COVID-19 pandemic.2 This work2 aligns with findings on which groups of citizens are more likely to comply with public health directives on mask usage and social distancing4-7 and broader findings on vaccine hesitancy outside of the COVID-19 context.8-13

Those previous works emphasize attitudinal and demographic correlates, but it is also possible that the characteristics of vaccines matter for vaccine hesitancy. Some research14-16 has shown that although people are unresponsive to the technology of the vaccine or the dosing regimen, they are more likely to take vaccine candidates that are domestically produced and with higher levels of safety and efficacy.

The previous studies14-16 tested people’s responsiveness to the characteristics of hypothetical vaccine candidates. However, the implications may well extend to the real world. Initial trials of AstraZeneca and Johnson & Johnson revealed less efficacy in preventing symptomatic COVID-19 compared with vaccines by Pfizer and Moderna. At the same time, these vaccines have relatively equal efficacy in preventing death and hospitalization from COVID-19,17,18 a factor that may be lost in the noise of competing public health directives for vaccine usage. Furthermore, regulators in Europe and North America have raised concerns about the association between AstraZeneca and, more recently, Johnson & Johnson and serious blood clots, which has been widely covered in the news media, possibly further undermining confidence.

Considering the importance of the Johnson & Johnson and AstraZeneca COVID-19 vaccines to global supply, identifying ways to mitigate hesitancy toward these specific vaccines is vitally important. Canada serves as a useful test case for these dynamics. The national regulator, Health Canada, has approved 4 COVID-19 vaccines (Moderna, Pfizer, AstraZeneca, and Johnson & Johnson), each with different usage guidelines, levels of availability, and safety and efficacy profiles. In this study, we examine whether providing information on the effectiveness of the AstraZeneca and Johnson & Johnson vaccines at preventing death from COVID-19 increases people’s confidence in their effectiveness and reduces their hesitancy toward these vaccines. We also explore whether this information can mitigate possible negative consequences that arise from providing information on the comparatively less-impressive record of these vaccines at preventing symptomatic COVID-19 infection.

Methods

This survey study was approved by the Social Science, Humanities, and Education Research Ethics Board at the University of Toronto. It was fielded from March 24 to 30, 2021, on an online nonprobability sample of adult Canadian citizens using the survey respondent panel provider Dynata, who use quota-based sampling to approximate nationally representative samples. In this case, quotas were set on age (ie, age 18-34, 35-54, and ≥55 years), gender (ie, male and female), region (ie, Atlantic, Quebec, Ontario, and West), and language (ie, English and French) to match population benchmarks in the 2016 Canadian census. Respondents were provided a consent form at the start of the survey and indicated their consent by proceeding to complete the survey. They could withdraw their consent at any time by closing their browser. The terms of compensation provided by Dynata to members of their panel and those who participated in our survey are proprietary. This study follows the American Association for Public Opinion Research (AAPOR) reporting guideline.

Although probability samples are needed for accurate estimates of the population, nonprobability samples perform well at studying associations between variables or for the estimation of sample average treatment effects, which is our focus here.19 Data are not weighted in the analyses that follow.

The study was a 2-by-2-by-2 factorial experiment. Respondents were randomly assigned into brand conditions using the Qualtrics survey platform (ie, AstraZeneca or Johnson & Johnson) and into conditions where they either received or did not receive information on the death prevention effectiveness of their assigned vaccine and its overall effectiveness at preventing symptomatic COVID-19. eTable 1 in the Supplement shows that random assignment was successful.

All respondents were given the following prime about their potential COVID-19 vaccine where the brand was randomly assigned: “Health Canada has recently approved the [AstraZeneca/Johnson & Johnson] vaccine.” Individuals in the control condition only received the preceding prime. Another group received additional information on the overall effectiveness of their randomly assigned vaccine at preventing cases of symptomatic COVID-19 where the number depended on whether they were assigned AstraZeneca (62%) or Johnson & Johnson (72%): “Studies have shown that the vaccine is [62%/72%] effective at preventing symptomatic COVID-19.” Another group instead received information that their assigned vaccine is virtually 100% effective at preventing death from COVID-19: “Studies have shown that the vaccine is nearly 100% effective at preventing death from COVID-19.” A final group received both pieces of information about their assigned vaccine.

All respondents were asked “How likely would you be to take this vaccine if offered to you?” (response categories: very likely, somewhat likely, not very likely, or not at all likely), and “How would you rate the effectiveness of the vaccine? (response categories: very effective, somewhat effective, not very effective, or not at all effective). The outcomes were rescaled from 0 to 1 so that higher values mean a higher likelihood of taking the vaccine and more confidence in its effectiveness.

We conducted a preregistered pilot of this study, fielded from March 8 to 18, 2021, using identical data collection procedures. The only difference in this design was the absence of brand information in the control condition. That pilot and its hypothesis testing can be found in the eAppendix and eFigure 1 in the Supplement.

Statistical Analysis

We preregistered expectations that vaccination intention and perceived effectiveness should be higher in the death prevention information conditions and lower in the overall efficacy conditions than when respondents were not given this information. We estimated a pair of models using ordinary least squares regression where we regressed intention and perceived effectiveness on binary variables for our overall efficacy and death prevention conditions, as follows: intention / effectiveness = α + β1death_info + β2efficacy_info + ε. It is also possible that providing one type of information attenuates the association of the other, so we then estimated another pair of models where we interacted our treatment conditions. We break our results down by brand in eFigure 2 in the Supplement: intention / effectiveness = α + β1death_info + β2efficacy_info + β3death_info × efficacy_info + ε.

In addition to our preregistered analysis, we conducted exploratory subgroup analyses to assess whether the association between the treatments and vaccination intention varied by demographic groups. Respondents self-identified their education, income, age, location of residence, gender, and race and ethnicity as part of the survey. These demographic variables were assessed to determine the associations between the treatment and vaccination intentions among different groups of respondents, which has implications for whom we should be targeting with persuasive messages regarding less-preferred vaccines. We estimated a series of models where we interacted both treatments with categorical variables for bachelor’s degree (designated as 1), middle income and high income (reference, low income), age 35 to 54 years old or 55 years and older (reference, 18-34 years), residence in a large city (designated as 1), visible membership in a racial or ethnic minority group (designated as 1), and gender (1 = female, 0 = male): intention = α + β1death_info + β2efficacy_info + β3moderator + β4death_info × moderator + β5efficacy_info × moderator + ε. Significance was set at P < .05 and was determined using 2-sided t tests. Data analysis was performed using Stata statistical software version 16 (StataCorp).

Results

The 2556 survey respondents had a median (IQR) age of 50 (34-63) years, and 1339 (52%) were women. A full comparison between the demographic characteristics of the sample and population benchmarks can be found in eTable 2 in the Supplement. The group means are provided in Figure 1. We found confirmation that intention (b, 0.04; 95% CI, 0.01 to 0.06; P = .004) and perceived vaccine effectiveness were higher for respondents given the death prevention information than for those who were not (b, 0.03; 95% CI, 0.01 to 0.05; P = .002). Intention (b, −0.03; 95% CI, −0.05 to −0.00; P = .03) and perceived effectiveness were also lower for those given information on the overall efficacy of their assigned vaccine compared with those who were not (b, −0.05; 95% CI, −0.08 to −0.03; P < .001).

We failed to find evidence of an interaction between the treatments—that is, providing one type of information did not appear to attenuate the association between receiving the other type and the outcomes, as shown in Figure 1. The associations between the death prevention information and the outcomes were the same whether or not a respondent received information about overall efficacy. Likewise, the negative association between overall efficacy information and outcomes remained whether or not a respondent received information about death prevention. Rather than overall efficacy and death prevention information interacting, their associations with the outcomes were additive. The model estimates are found in eTable 3 in the Supplement. The outcomes were not continuous, so for robustness we estimated our models using ordinal logistic regression. These estimates are provided in eTable 4 in the Supplement, and the results for the interaction model are graphically presented in eFigure 3 in the Supplement.

Our exploratory subgroup analyses identified 2 important moderators of the death prevention treatment on intention: age and gender. The full estimates for our subgroup analyses are provided in Table 1 and Table 2. We illustrate the results graphically with linear estimates in Figure 2. Among respondents aged 35 to 54 years, intention was 0.08 point higher on a 0 to 1 scale for those given the death prevention information compared with those who were not (95% CI, 0.04 to 0.12; P < .001), whereas there was no significant difference between the conditions among those younger than 35 years (b, 0.00; 95% CI, −0.05 to 0.06; P = .81) and those older than 54 years (b, 0.02; 95% CI, −0.02 to 0.06; P = .39). The result is that the gap in intention between middle-aged and older respondents was markedly smaller in the treatment condition compared with the control, as shown in Figure 2.

Among women, intention was also 0.07 point higher for those given the death prevention information compared with those who were not (95% CI, 0.04 to 0.11; P < .001), whereas there was no significant difference among men (b, −0.00; 95% CI, −0.04 to 0.04; P = .93). The result is that the gap in intention between men and women is considerably smaller in the treatment condition, as shown in Figure 2. We found no significant subgroup differences in the associations between the provision of overall efficacy information treatment and vaccination intention.

It is worth noting that in Canada, AstraZeneca’s vaccine was targeted first toward people aged 50 to 55 years, then those aged 40 to 55 years, and finally those aged 30 to 55 years. It is this group for whom AstraZeneca was most relevant. We analyzed our results for age and gender by brand and found that the result for age (but not gender) was found exclusively for those in the AstraZeneca condition. These results are presented graphically in eFigure 4 in the Supplement.

Discussion

In a context of rapidly changing and sometimes contradictory advisories on the use of COVID-19 vaccines, this survey study found that individuals were not favorably disposed toward those produced by AstraZeneca and Johnson & Johnson. This was true in a national context (Canada), where several vaccines have been approved but are not equally available to all citizens.

It is an open question whether such brand preferences would exist absent the potential of receiving another vaccine. It is also an open question, given brand preferences, whether countries may actually slow down vaccination rates by procuring multiple types of vaccine, only some of which citizens will be willing to take if the potential of waiting for another vaccine exists. Nonetheless, given the importance of the Johnson & Johnson, and especially AstraZeneca, vaccines to global supply, mitigating hesitancy toward these vaccines is vitally important.

We found that providing information to respondents about the effectiveness of AstraZeneca or Johnson & Johnson at preventing death from COVID-19 was associated with more confident beliefs in the effectiveness of their assigned vaccine and more willingness to take it if offered. This appeared to be true particularly among middle-aged respondents for whom AstraZeneca was targeted, as well as women. On the other hand, providing individuals with information on the comparatively less-impressive ability of their assigned vaccine to prevent any symptomatic COVID-19 infection was associated with less confidence in its effectiveness and less willingness to take it if offered. Unfortunately, information about the impressive record of AstraZeneca and Johnson & Johnson at death prevention did not appear counteract the negative association between providing information on their overall efficacy and perceived effectiveness or intention to vaccinate. Both pieces of information simply canceled each other out. This suggests that there is a need to focus communication strategies on this metric of performance rather than the arguably less important indicator of overall effectiveness at preventing symptomatic COVID-19.

There may well be other ways to tailor this type of message for greater effectiveness. Rather than speaking of vaccine effectiveness in terms of percentages, science communicators can use plain language or graphical images to convey the effectiveness of the AstraZeneca and Johnson & Johnson vaccines. It is also possible that neutralizing information—such as explaining the substantive limitations of overall efficacy information—may counteract the effects of this information when provided in isolation, because people may not fully understand what information this metric is conveying to them. Of course, individuals can also be persuaded to vaccinate with messages that are not based on scientific data, such as appeals to norms and values or compelling narratives from individuals who have received AstraZeneca or Johnson & Johnson that account for why they did so.

Researchers can also experiment with different sources to convey these messages. Skepticism toward AstraZeneca and Johnson & Johnson has resulted from highly flawed communication of rare adverse effects through the news media. Scientists, doctors, and medical professionals are highly credible sources who could potentially enhance the persuasive potential of messages aimed at conveying the benefits of these vaccines. We encourage future research on alternative communication strategies that can enhance uptake of less-preferred COVID-19 vaccines.

Limitations

There are a few important limitations to the data and design we present here. First, this study was conducted on an online nonprobability sample of Canadian adults. We cannot make strong claims to population generalizability. Nonetheless, the demographic characteristics of our sample closely match important population benchmarks (see eTable 2 in the Supplement), and observed treatment effects do not usually differ markedly between probability and nonprobability samples.19 Second, Canada is characterized by a unique dynamic where multiple COVID-19 vaccines were approved and procured with uneven access to each of them throughout the population. Other countries have different vaccines procured in varying relative quantities and have different rollout strategies. Seeing how these results travel cross-nationally is important, especially to contexts that are reliant on the AstraZeneca and Johnson & Johnson vaccines.

Third, it is worth noting that surveys can only indirectly shed light on behavior through self-reported measures. Whether providing information about the death prevention potential of AstraZeneca and Johnson & Johnson actually improves uptake of these vaccines in the real world is a nearly impossible question to address with survey research. Fourth, it is worth noting that the interventions tested here are based on metrics from trial data featuring the original strain of COVID-19. The rise of the variants has changed the efficacy profile of the COVID-19 vaccines, and more data are now available on their real-world effectiveness. Effectively communicating information about the safety and efficacy profiles of different vaccines during rapidly evolving conditions is an enormous challenge.

Conclusions

By use of a between-participants experiment included in a survey of Canadian adults randomly assigned vaccine brand conditions, we found that providing information on the effectiveness of less-preferred vaccines like AstraZeneca and Johnson & Johnson at preventing death from COVID-19 was associated with more confidence in the effectiveness of these vaccines and more willingness to take them if offered. Information on the overall effectiveness of these vaccines at preventing symptomatic COVID-19 infection showed the opposite result. Providing information related to death prevention ability of these vaccines did not, however, mitigate the negative association between the provision of overall efficacy information and perceptions of their effectiveness or willingness to take them if offered. These results can inform public health communication strategies to reduce hesitancy toward specific COVID-19 vaccines.

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Article Information

Accepted for Publication: July 22, 2021.

Published: September 30, 2021. doi:10.1001/jamanetworkopen.2021.26635

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Merkley E et al. JAMA Network Open.

Corresponding Author: Peter John Loewen, PhD, Munk School of Global Affairs and Public Policy, University of Toronto, One Devonshire Pl, Toronto, ON M5S 3K7, Canada (peter.loewen@utoronto.ca).

Author Contributions: Drs Merkley and Loewen had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Merkley.

Acquisition, analysis, or interpretation of data: Both authors.

Drafting of the manuscript: Merkley.

Critical revision of the manuscript for important intellectual content: Both authors.

Statistical analysis: Merkley.

Obtained funding: Loewen.

Administrative, technical, or material support: Loewen.

Supervision: Loewen.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was supported by grants from 19toZero, the Department of Canadian Heritage, and the University of Toronto to Drs Merkley and Loewen.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: Jamie Druckman, PhD (Northwestern University), and members of the Policy, Election, and Representation Lab provided helpful comments on earlier drafts of this manuscript. They were not compensated beyond their normal salaries.

Additional Information: A preanalysis plan for this study was registered on the Open Science Foundation (see https://osf.io/74e2x).

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Gene found in monkeys and mice could work as a new type of antiviral to block HIV, Ebola, and other deadly viruses in humans


Peer-Reviewed Publication

UNIVERSITY OF UTAH HEALT

A nationwide team of researchers, led by scientists at University of Utah Health and The Rockefeller University, has determined how a genetic mutation found in mice and monkeys interferes with viruses such as HIV and Ebola. They say the finding could eventually lead to the development of medical interventions in humans.

The gene, called retroCHMP3, encodes an altered protein that disrupts the ability of certain viruses to exit an infected cell and prevents it from going on to infect other cells.

Normally, some viruses encase themselves in cell membranes and then make an exit by budding off from the host cell. RetroCHMP3 delays that process long enough that the virus can no longer escape.

“This was an unexpected discovery,” says Nels Elde, Ph.D., senior author of the study and an evolutionary geneticist in the Department of Human Genetics at U of U Health. “We were surprised that slowing down our cell biology just a little bit throws virus replication off its game.”

The study appears online Sept. 30 in advance of the Oct. 14 issue of Cell.

RetroCHMP3 originated as a duplicated copy of a gene called charged multivesicular body protein 3, or CHMP3. While some monkeys, mice, and other animals have retroCHMP3 or other variants, humans only have the original CHMP3.

In humans and other creatures, CHMP3 is well known for playing a key part of a role in cellular processes that are vital for maintaining cellular membrane integrity, intercellular signaling, and cell division.

HIV and certain other viruses hijack this pathway to bud off from the cellular membrane and infect other cells. Based on their research, Elde and his colleagues suspected that the duplications of CHMP3 they discovered in primates and mice blocked this from happening as protection against viruses like HIV and other viral diseases.

Building on this notion, Elde and other scientists began exploring whether variants of retroCHMP3 might work as an antiviral. In laboratory experiments conducted elsewhere, a shorter, altered version of human CHMP3 successfully prevented HIV from budding off cells. But there was a glitch: the modified protein also disrupted important cellular functions, causing the cells to die.

Unlike the other researchers, Elde and his colleagues at U of U Health had naturally occurring variants of CHMP3 from other animals in hand. So, working in collaboration with researchers Sanford Simon at The Rockefeller University, along with Phuong Tieu Schmitt and Anthony Schmitt at Pennsylvania State University, they tried a different approach.

Using genetic tools, they coaxed human cells to produce the version of retroCHMP3 found in squirrel monkeys. Then, they infected the cells with HIV and found that the virus had difficulty budding off from the cells, essentially stopping them in their tracks. And this occurred without disrupting metabolic signaling or related cellular functions that can cause cell death. 

“We’re excited about the work because we showed some time ago that many different enveloped viruses use this pathway, called the ESCRT pathway, to escape cells,” says Wes Sundquist, Ph.D., a co-corresponding author of the study and chair of the Department of Biochemistry at the University of Utah. “We always thought that this might be a point at which cells could defend themselves against such viruses, but we didn’t see how that could happen without interfering with other very important cellular functions.”

From an evolutionary perspective, Elde believes this represents a new type of immunity that can arise quickly to protect against short-lived threats.

“We thought the ESCRT pathway was an Achilles heel that viruses like HIV and Ebola could always exploit as they bud off and infect new cells,” Elde says. “RetroCHMP3 flipped the script, making the viruses vulnerable. Moving forward, we hope to learn from this lesson and use it to counter viral diseases.”

More specifically, that lesson “raises the possibility that an intervention that slows down the process may be inconsequential for the host, but provide us with a new anti-retroviral,” says Sanford Simon, Ph.D, a study co-author and  a professor of Cellular Biophysics at The Rockefeller University.

                                                ###

In addition to Drs. Elde and Sundquist, University of Utah and University of Utah Health scientists Lara Rheinemann, Diane Miller Downhour, Gaelle Mercenne, Kristen Davenport, Christina Necessary, and John McCullough contributed to this study.

 

The study, “RetroCHMP3 Blocks Budding of Enveloped Viruses Without Blocking Cytokinesis,” appears in the October 14, 2021 issue of Cell. This research was supported by the National Institutes of Health, United States Department of Agriculture, the Burroughs Wellcome Fund, and a Pew Charitable Trusts Innovation Fund Award.

A nationwide team of researchers, led by scientists at University of Utah Health and The Rockefeller University, has determined how a genetic mutation found in mice and monkeys interferes with viruses such as HIV and Ebola. They say the finding could eventually lead to the development of medical interventions in humans.

The gene, called retroCHMP3, encodes an altered protein that disrupts the ability of certain viruses to exit an infected cell and prevents it from going on to infect other cells.

Normally, some viruses encase themselves in cell membranes and then make an exit by budding off from the host cell. RetroCHMP3 delays that process long enough that the virus can no longer escape.

“This was an unexpected discovery,” says Nels Elde, Ph.D., senior author of the study and an evolutionary geneticist in the Department of Human Genetics at U of U Health. “We were surprised that slowing down our cell biology just a little bit throws virus replication off its game.”

The study appears online Sept. 30 in advance of the Oct. 14 issue of Cell.

RetroCHMP3 originated as a duplicated copy of a gene called charged multivesicular body protein 3, or CHMP3. While some monkeys, mice, and other animals have retroCHMP3 or other variants, humans only have the original CHMP3.

In humans and other creatures, CHMP3 is well known for playing a key part of a role in cellular processes that are vital for maintaining cellular membrane integrity, intercellular signaling, and cell division.

HIV and certain other viruses hijack this pathway to bud off from the cellular membrane and infect other cells. Based on their research, Elde and his colleagues suspected that the duplications of CHMP3 they discovered in primates and mice blocked this from happening as protection against viruses like HIV and other viral diseases.

Building on this notion, Elde and other scientists began exploring whether variants of retroCHMP3 might work as an antiviral. In laboratory experiments conducted elsewhere, a shorter, altered version of human CHMP3 successfully prevented HIV from budding off cells. But there was a glitch: the modified protein also disrupted important cellular functions, causing the cells to die.

Unlike the other researchers, Elde and his colleagues at U of U Health had naturally occurring variants of CHMP3 from other animals in hand. So, working in collaboration with researchers Sanford Simon at The Rockefeller University, along with Phuong Tieu Schmitt and Anthony Schmitt at Pennsylvania State University, they tried a different approach.

Using genetic tools, they coaxed human cells to produce the version of retroCHMP3 found in squirrel monkeys. Then, they infected the cells with HIV and found that the virus had difficulty budding off from the cells, essentially stopping them in their tracks. And this occurred without disrupting metabolic signaling or related cellular functions that can cause cell death. 

“We’re excited about the work because we showed some time ago that many different enveloped viruses use this pathway, called the ESCRT pathway, to escape cells,” says Wes Sundquist, Ph.D., a co-corresponding author of the study and chair of the Department of Biochemistry at the University of Utah. “We always thought that this might be a point at which cells could defend themselves against such viruses, but we didn’t see how that could happen without interfering with other very important cellular functions.”

From an evolutionary perspective, Elde believes this represents a new type of immunity that can arise quickly to protect against short-lived threats.

“We thought the ESCRT pathway was an Achilles heel that viruses like HIV and Ebola could always exploit as they bud off and infect new cells,” Elde says. “RetroCHMP3 flipped the script, making the viruses vulnerable. Moving forward, we hope to learn from this lesson and use it to counter viral diseases.”

More specifically, that lesson “raises the possibility that an intervention that slows down the process may be inconsequential for the host, but provide us with a new anti-retroviral,” says Sanford Simon, Ph.D, a study co-author and  a professor of Cellular Biophysics at The Rockefeller University.

### 

In addition to Drs. Elde and Sundquist, University of Utah and University of Utah Health scientists Lara Rheinemann, Diane Miller Downhour, Gaelle Mercenne, Kristen Davenport, Christina Necessary, and John McCullough contributed to this study.

The study, “RetroCHMP3 Blocks Budding of Enveloped Viruses Without Blocking Cytokinesis,” appears in the October 14, 2021 issue of Cell. This research was supported by the National Institutes of Health, United States Department of Agriculture, the Burroughs Wellcome Fund, and a Pew Charitable Trusts Innovation Fund Award.

 

Sexual minority identity impacts career trajectory among medical students


Peer-Reviewed Publication

UNIVERSITY OF MINNESOTA MEDICAL SCHOOL

The conversation surrounding equal rights for the LGBTQ+ community has recently been in the political spotlight in the U.S. But, despite advances in civil rights, this population continues to suffer from unique disparities among both patients and healthcare providers.

A study co-authored by Matthew Mansh, MD, corresponding author and a dermatologist with the University of Minnesota Medical School and M Health Fairview, published today on the JAMA Network aimed to assess the distribution of sexual minorities by intended specialty among graduating medical students. The researchers’ results show that not only are sexual minority people underrepresented within undergraduate medical training, but that there are disparities in which fields they intend to pursue after graduating. 

“Sexual minorities face numerous health disparities, including poor access to knowledgeable providers and culturally-sensitive care,” Mansh said. “Workforce diversity is essential to ensure a pipeline of physicians equipped through personal experiences and diverse learning environments to improve care for sexual minority people, but little is known about sexual orientation diversity in medical training.”

The study analyzed de-identified, self-reported data between 2016 and 2019 from the Association of American Medical Colleges Graduate Questionnaire. They compiled the following key statistics:

  • Only 5.7% of female medical students identified as sexual minority, compared to an estimated 9.4% of young females in the general population who identify as sexual minority.. 
  • Sexual minority female medical students were less likely to intend to practice in primary care specialties and more likely to want to practice in surgical specialties as compared to their heterosexual female peers.
  • Sexual minority male medical students were less likely to intend to practice in surgical specialties and more likely in primary care specialties as compared to their heterosexual male peers. 

The researchers concluded that sexual minority people — specifically sexual minority females — are underrepresented in undergraduate medical training and also in the workforce pipeline towards certain specialties. But, overall, sexual minority diversity varied significantly between specialties.

Further research is needed to better understand the causes of these disparities, including the impact of specialty-specific training environments, such as perceived inclusivity and/or trainee  mistreatment.

“Sexual orientation data collection should be standardized in all physician workforce surveys and sexual minority diversity should be considered in undergraduate and graduate medical training recruitment to promote a diverse physician workforce across all specialties,” Mansh said.

Co-authors of this study are Westly S. Mori, MD, and Yi Gao, MD, of the U of M Medical School; Eleni Linos, MD, MPH, DrPH; Mitchell R. Lunn, MD, MAS; Juno Obedin-Maliver, MD, MPH, MAS, of the Stanford University School of Medicine; and Howa Yeung, MD, MSC, of the Emory University School of Medicine. 

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About the University of Minnesota Medical School
The University of Minnesota Medical School is at the forefront of learning and discovery, transforming medical care and educating the next generation of physicians. Our graduates and faculty produce high-impact biomedical research and advance the practice of medicine. We acknowledge that the U of M Medical School, both the Twin Cities campus and Duluth campus, is located on traditional, ancestral and contemporary lands of the Dakota and the Ojibwe, and scores of other Indigenous people, and we affirm our commitment to tribal communities and their sovereignty as we seek to improve and strengthen our relations with tribal nations. For more information about the U of M Medical School, please visit med.umn.edu

Satirical essay critiques power imbalances in global health research


Reports and Proceedings

PLOS

Satirical essay critiques power imbalances in global health research 

IMAGE: INTERNATIONAL COLLABORATIONS CAN HELP OR HINDER BIOMEDICAL RESEARCH FOR GLOBAL HEALTH view more 

CREDIT: OKEKE, I. N., MEDICINE ANTHROPOLOGY THEORY, CC-BY 4.0 (HTTPS://CREATIVECOMMONS.ORG/LICENSES/BY/4.0/)

When establishing partnerships with research counterparts in under-resourced countries, global health researchers often deploy discourse that claims to focus on sustainability and capacity building. But how is this viewed from the other side of the partnership? A satirical opinion article publishing September 30th in PLOS Biology by Iruka Okeke of University of Ibadan, Nigeria, highlights the extractive and exploitive aspects of health research partnerships between biomedical researchers in high-income countries and their counterparts in low-income, disease-endemic countries.

The actual short- and long-termed benefits of these collaborations may be one-sided. In her essay entitled “Twenty steps to ingrain power asymmetry in global health biomedical research,” the author uses the global health lexicon as a rhetorical aid to offer a counter-perspective on research collaborations in low-income countries initiated and implemented by scientists from high-income countries. The twenty steps spotlight twenty problematic practices of global health researchers that may maintain and exacerbate inequities in health research.

According to the author, “Are you a laboratory scientist par excellence with international research ambitions? As my tip list draws on common stereotypes, I’ll presume that you are a high-income country scientist with low-income country research aspirations.” Among her twenty hot tips for success, Dr Okeke has this handy advice: “Pick a Partner Country. Avoid locations where good research in the area has previously been conducted. Instead prioritize countries with pristine beaches, a game reserve or some other ‘must see’. Holiday brochures could be helpful at this stage.”

Okeke adds, “This satire chronicles unfortunate but common intentional and unintentional collaboration missteps that can compromise the sustainability and impact of global health laboratory projects.”

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In your coverage please use these URLs to provide access to the freely available articles in PLOS Biology http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001411

Citation: Okeke IN (2021) Twenty steps to ingrain power asymmetry in global health biomedical research. PLoS Biol 19(9): e3001411. https://doi.org/10.1371/journal.pbio.3001411

Funding: The author received no specific funding for this work.

 

Toxic algae blooms are getting worse, but oversight is lacking

Toxic algae blooms are getting worse, but oversight is lacking
This satellite image shows the deep green of an algae bloom on Lake Erie on
 30 July 2019. Credit: Goddard Space Flight Center, NASA

Poisonous algae blooms are becoming more common in the US, threatening water supplies and public health. But so far, there are few state or federal guidelines, and local water managers could use some help, a UConn-led team of researchers reports in the September 30 issue of Nature Sustainability.

A massive bloom of green-blue  in Lake Erie in 2014 forced Toledo, Ohio to warn over half a million residents not to drink or even touch their tap water. It was one of the first times that  made national news, but it wouldn't be the last. Since then, Salem, Oregon; Lake Hodges in California; and Lake Oneida in New York have had massive blooms. The toxins produced by such blooms can cause numbness, dizziness, convulsions, liver damage and even death.

"They're nasty," says Christine Kirchhoff, Associate Professor and Castleman Professor of Engineering Innovation in the Department of Civil & Environmental Engineering. Some of these toxins, such as liver-damaging microcystins and cylindrospermopsin, can be managed with combinations of chlorine and activated carbon. Other algae toxins like anatoxins and saxitoxins, which target the nervous system, are not easily removed by conventional water treatments. And you can't boil them out of the water. So when a big algae bloom occurs in a reservoir, water managers can struggle to make sure the water is safe.

Kirchhoff and other researchers from UConn and the University of Michigan surveyed public water managers across the United States who manage systems that draw from inland lakes. Such lakes, even extremely large ones such as Lake Erie, are warming and may become more prone to algae blooms due to climate change.

More than half the water managers surveyed said their system had experienced a bloom of harmful algae at least once. Almost a third of the managers said they experienced them at least once a year, and 60% of those who'd had a bloom said they believed the problem was getting worse. Most water managers said they relied on their state agencies and professional associations for advice on how to handle harmful algae blooms in the water supply.

Unfortunately, a lot of state agencies don't have that much to offer on the problem. States take their cues from the US Environmental Protection Agency (EPA), and currently EPA doesn't regulate algae toxins under the Safe Drinking Water Act. Through the Unregulated Contaminant Monitoring Program, EPA did collect data from the treated water of a random sample of water systems across the US a few years ago, and the results showed limited occurrence of toxins in public .

Kirchhoff says the EPA survey aims to be nationally representative and so cannot rule out the potential for greater risk of toxic blooms at a state or regional level. The Connecticut Department of Public Health had a voluntary  toxin testing program after the Toledo bloom raised concerns in the state. Systems that submitted voluntary samples for testing did not detect any toxins, and the testing program was discontinued.

Because cyanobacteria behavior is complex, monitoring for algal toxins is also complicated. Sometimes there is no visible bloom, but there are toxins present or there may be toxins in one part of a lake or at one depth and not elsewhere. For these reasons, "I would like to see a longer term, broader monitoring program that uses what we know now," to determine areas at risk here in Connecticut and across the country, to better protect the public, Kirchhoff says.

Toxic algae reported in Yosemite Valley creek
More information: Treuer, G. et al. Challenges of managing harmful algal blooms in US drinking water systems. Nat Sustain (2021). doi.org/10.1038/s41893-021-00770-y
Journal information: Nature Sustainability 
Provided by University of Connecticut 

 

Racial/ethnic disparities in childhood

 cancer survival in the United States


Peer-Reviewed Publication

AMERICAN CANCER SOCIETY

ATLANTA – SEPTEMBER 30, 2021 – A new study finds racial/ethnic disparities in survival among newly diagnosed patients with childhood cancers in the United States and that area-level socioeconomic status (SES) and health insurance contribute to these disparities. The study, appearing in Cancer Epidemiology, Biomarkers & Prevention Survival, found that compared to non-Hispanic (NH) White childhood cancer patients, NH Black and Hispanic patients had worse survival for all cancers combined, leukemias and lymphomas, brain tumors, and solid tumors. The study was based on data from children (aged <18 years) newly diagnosed with cancer during 2004 to 2015 in a nationwide hospital-based cancer registry.

To learn more about these disparities, investigators led by Jingxuan Zhao, MPH, American Cancer Society, evaluated modifiable factors that contribute to racial/ethnic disparities in childhood cancer survival. They found that survival disparities were reduced after adjusting for health insurance and area-level SES separately, and further reduced after adjusting for both together.

Since the 1970s, 5-year survival of childhood cancer has improved dramatically to 80%, largely driven by the widespread participation in clinical trials (nearly 60%), improved supportive care, and development of new therapies. However, improvements in survival have not been experienced equally in all race/ethnicity groups. For example, clinical trial participation rates have been low for minority children with cancer, which could be possibly explained by barriers resulting from lower SES and being uninsured.

Historically, non-white childhood cancer patients were overrepresented in the lower SES stratum, which is associated with problems with health care access and affordability potentially due to a complex interplay of their parents’ financial status, employment, and health literacy. In this study, NH Black and Hispanic childhood cancer patients were more likely to be uninsured or be covered by Medicaid than NH White patients. Being uninsured has been linked to delays in receiving timely care and completing care, and as a result, may lead to worse survival.

“This study suggests that improving health insurance coverage and access to care for children, especially those with low SES, may reduce racial/ethnic survival disparities,” write the authors. “This continued inequity in health outcomes among children warrants concerted, multifaceted approaches to address and minimize these disparities in the future.”

Article: Zhao J, Han X, Zheng Z, Nogueira L, Lu AD, Nathan PC, Yabroff KR. Racial/ethnic disparities in childhood cancer survival in the United States. Cancer Epidemiology, Biomarkers & Prevention Survival. doi: 10.1158/1055-9965.EPI-21-0117.

URL upon embargo: https://cebp.aacrjournals.org/content/early/2021/09/16/1055-9965.EPI-21-0117.

Study shows ethnicity plays role in NHS staff decisions to speak up

30 SEPTEMBER, 2021 BY EMMA BAINES
NURSING TIMES



NHS staff from Black and minority ethnic groups continue to face barriers speaking up about workplace issues, according to research reported by the National Guardian’s Office (NGO) today.

Research commissioned by the NGO found that minority ethnic staff were less likely than White staff members to voice concerns to a Freedom to Speak Up Guardian of a different ethnicity from themselves, because they feared their concern would not be understood or taken seriously.


“All staff should feel confident that their workplace processes are fair and should not fear reprisals"
Habib Naqvi


This presents a barrier to minority ethnic staff flagging discrimination or other workplace issues through the Guardian network at all, because Freedom to Speak Up Guardians are predominantly White.

The research report, Difference Matters, includes data from an online survey of 1,074 workers from eight NHS trusts, 69% of whom were White and 31% Black or minority ethnic.

Over 55% of the survey respondents reported experiencing an issue within the previous four years that they felt could have been raised with a Freedom to Speak Up Guardian. Of these, more minority ethnic (62%) than White (57%) people chose not to raise their concern with a Guardian.

A large difference between the groups was that a much higher proportion of minority ethnic respondents reported that their issues were relating to discrimination (55%) compared to White respondents (8%).

Because of this, 41% of minority ethnic staff reported that they would like to be able to speak to a Guardian of the same ethnicity as themselves. They feared someone else would not understand their concern, or take it seriously. In comparison, only 7% of White respondents said they wanted a Guardian of the same ethnicity.

However, the network of Freedom to Speak Up Guardians is disproportionately White compared to the NHS workforce, with only 10% of Guardians having a minority ethnic background in 2020, down by a third from 2019, according to the most recent NGO’s Freedom to Speak Up Survey.

The research found that Black and minority ethnic workers who did speak up had comparable experiences to White workers.

The report stated: “Based on the responses to the survey and feedback from Freedom to Speak Up Guardians, we conclude that the ethnicity of a Freedom to Speak Up Guardian can impact on a person’s decision to speak up. Specifically, BME workers are more likely to raise a concern with a BME Freedom to Speak Up Guardian.”

“It is clear that more work needs to be done to explore the many factors that can influence whether, when, and to whom a worker will speak up"
Russell Parkinson

Dr Habib Naqvi, director of the NHS Race and Health Observatory, said: “It is important that Black and minority ethnic health and care staff feel confident about speaking up and disclosing information that can prevent avoidable incidents, and lead to better care and outcomes for patients.

“All staff should feel confident that their workplace processes are fair and should not fear reprisals, or the prospect of being discriminated against, for voicing concerns through official channels.

“The healthcare system needs to take targeted action, ensuring opportunities to learn important lessons regarding patient care are not missed.”

Russell Parkinson, head of office and strategy at the NGO, said the research was a “starting place for further discussion”.

“It is clear that more work needs to be done to explore the many factors that can influence whether, when, and to whom a worker will speak up,” he added.

The Freedom to Speak Up Guardians were established so that NHS staff would have an alternative route for raising concerns if they feel unable to do so through the usual channels, such as telling a line manager.

There are now more than 700 Guardians supporting workers in primary and secondary care as well as other NHS organisations.

The NHS People Plan includes commitments to recruit more staff from Black and minority ethnic backgrounds to Guardian roles and to improve training for Guardians on workplace race equality.