Considerations for stakeholder engagement and COVID‐19 related clinical trials’ conduct in sub‐Saharan Africa

The aim of this study is to determine how stakeholder engagement can be adapted for the conduct of COVID‐19‐related clinical trials in sub‐Saharan Africa. Nine essential stakeholder engagement practices were reviewed: formative research; stakeholder engagement plan; communications and issues management plan; protocol development; informed consent process; standard of prevention for vaccine research and standard of care for treatment research; policies on trial‐related physical, psychological, financial, and/or social harms; trial accrual, follow‐up, exit trial closure and results dissemination; and post‐trial access to trial products or procedures. The norms, values, and practices of collectivist societies in Sub‐Saharan Africa and the low research literacy pose challenges to the conduct of clinical trials. Civil‐society organizations, members of community advisory boards and ethics committees, young persons, COVID‐19 survivors, researchers, government, and the private sector are assets for the implementation and translation of COVID‐19 related clinical trials. Adapting ethics guidelines to the socio‐cultural context of the region can facilitate achieving the aim of stakeholder engagement.     

Towards a Science of Community Stakeholder Engagement in Biomedical HIV Prevention Trials: An Embedded Four-Country Case Study

Objectives

Broad international guidelines and studies in the context of individual clinical trials highlight the centrality of community stakeholder engagement in conducting ethically rigorous HIV prevention trials. We explored and identified challenges and facilitators for community stakeholder engagement in biomedical HIV prevention trials in diverse global settings. Our aim was to assess and deepen the empirical foundation for priorities included in the GPP guidelines and to highlight challenges in implementation that may merit further attention in subsequent GPP iterations.

Methods

From 2008–2012 we conducted an embedded, multiple case study centered in Thailand, India, South Africa and Canada. We conducted in-depth interviews and focus groups with respondents from different trial-related subsystems: civil society organization representatives, community advocates, service providers, clinical trialists/researchers, former trial participants, and key HIV risk populations. Interviews/focus groups were recorded, and coded using thematic content analysis. After intra-case analyses, we conducted cross-case analysis to contrast and synthesize themes and sub-themes across cases. Lastly, we applied the case study findings to explore and assess UNAIDS/AVAC GPP guidelines and the GPP Blueprint for Stakeholder Engagement.

Results

Across settings, we identified three cross-cutting themes as essential to community stakeholder engagement: trial literacy, including lexicon challenges and misconceptions that imperil sound communication; mistrust due to historical exploitation; and participatory processes: engaging early; considering the breadth of “community”; and, developing appropriate stakeholder roles. Site-specific challenges arose in resource-limited settings and settings where trials were halted.

Conclusions

This multiple case study revealed common themes underlying community stakeholder engagement across four country settings that largely mirror GPP goals and the GPP Blueprint, as well as highlighting challenges in the implementation of important guidelines. GPP guidance documents could be strengthened through greater focus on: identifying and addressing the community-specific roots of mistrust and its impact on trial literacy activities; achieving and evaluating representativeness in community stakeholder groups; and addressing the impact of power and funding streams on meaningful engagement and independent decision-making.     

Ethics and HIV prevention research: An analysis of the early tenofovir PrEP trial in Nigeria

In 2004, the first ever multi‐sited clinical trials studied the prospect of HIV biomedical prevention (referred to as pre‐exposure prophylaxis—‘PrEP’). The trials were implemented at several international sites, but many officially closed down before they completed. At most sites, both scientists and community AIDS advocates raised concerns over the ethics and scientific rationales of the trial. Focusing on the Nigerian trial site, we detail the controversy that emerged among mostly Nigerian research scientists who scrutinized the research design and protocol. While some of the disputes, especially those pertaining to community engagement mechanisms, were ultimately resolved in international fora and implemented in later PrEP trials, concerns over science rationales and assumptions were never addressed. We argue that scientific rationales should be treated as ethical concerns and suggest that such concerns should be deliberated at host sites before the trial protocol is finalized.     

The 12th International Workshops on Opportunistic Protists (IWOP‐12)

The 12th International Workshops on Opportunistic Protists (IWOP‐12) was held in August 2012 in Tarrytown, New York. The objectives of the IWOP meetings are to: (1) serve as a forum for exchange of new information among active researchers concerning the basic biology, molecular genetics, immunology, biochemistry, pathogenesis, drug development, therapy, and epidemiology of these immunodeficiency‐associated pathogenic eukaryotic microorganisms that are seen in patients with AIDS and (2) foster the entry of new and young investigators into these underserved research areas. The IWOP meeting focuses on opportunistic protists, e.g. the free‐living amoebae, Pneumocystis, Cryptosporidium, Toxoplasma, the Microsporidia, and kinetoplastid flagellates. This conference represents the major conference that brings together research groups working on these opportunistic pathogens. Slow but steady progress is being achieved on understanding the biology of these pathogenic organisms, their involvement in disease causation in both immune‐deficient and immune‐competent hosts, and is providing critical insights into these emerging and reemerging pathogens. This IWOP meeting demonstrated the importance of newly developed genomic level information for many of these pathogens and how analysis of such large data sets is providing key insights into the basic biology of these organisms. A great concern is the loss of scientific expertise and diversity in the research community due to the ongoing decline in research funding. This loss of researchers is due to the small size of many of these research communities and a lack of appreciation by the larger scientific community concerning the state of art and challenges faced by researchers working on these organisms.     

Research ethics education for community-engaged research: a review and research agenda

Community engagement is increasingly becoming an integral part of research. "Community-engaged research" (CEnR) introduces new stakeholders as well as unique challenges to the protection of participants and the integrity of the research process. We--a group of representatives of CTSA-funded institutions and others who share expertise in research ethics and CEnR--have identified gaps in the literature regarding (1) ethical issues unique to CEnR; (2) the particular instructional needs of academic investigators, community research partners, and IRB members; and (3) best practices for teaching research ethics. This paper presents what we know, as well as what we still need to learn, in order to develop quality research ethics educational materials tailored to the full range of stakeholder groups in CEnR.     

A new scyphozoan from the Cambrian Fortunian Stage of South China

Animals with radial symmetry are abundant in the Cambrian Fortunian Stage of South China, but with relatively low diversity: representatives include Olivooides, Quadrapyrgites, carinachitiids, hexangulaconulariids and Pseudooides. Here, we report a new radial animal, Qinscyphus necopinus gen. et sp. nov., from the Fortunian small shelly fauna of southern Shaanxi Province, South China. Qinscyphus necopinus has a cup‐shaped profile, with slightly raised annuli and five groups of triangular thickenings in pentaradial symmetry. This organism has a comparable morphology to, and thus a close affinity with, Olivooides and Quadrapyrgites, and is interpreted as a coronate scyphozoan. This discovery adds a new crown‐group cnidarian to the Cambrian Explosion.     

Co‐occurrence of bobcats,coyotes, and ocelots in Texas

Interspecific competition among carnivores has been linked to differences in behavior, morphology, and resource use. Insights into these interactions can enhance understanding of local ecological processes that can have impacts on the recovery of endangered species, such as the ocelot (Leopardus pardalis). Ocelots, bobcats (Lynx rufus), and coyotes (Canis latrans) share a small geographic range overlap from South Texas to south‐central Mexico but relationships among the three are poorly understood. From May 2011 to March 2018, we conducted a camera trap study to examine co‐occurrence patterns among ocelots, bobcats, and coyotes on the East Foundation's El Sauz Ranch in South Texas. We used a novel multiseason extension to multispecies occupancy models with ≥2 interacting species to conduct an exploratory analysis to examine interspecific interactions and examine the potential effects of patch‐level and landscape‐level metrics relative to the occurrence of these carnivores. We found strong evidence of seasonal mutual coexistence among all three species and observed a species‐specific seasonal trend in detection. Seasonal coexistence patterns were also explained by increasing distance from a high‐speed roadway. However, these results have important ecological implications for planning ocelot recovery in the rangelands of South Texas. This study suggests a coexistence among ocelots, bobcats, and coyotes under the environmental conditions on the El Sauz Ranch. Further research would provide a better understanding of the ecological mechanisms that facilitate coexistence within this community. As road networks in the region expand over the next few decades, large private working ranches will be needed to provide important habitat for ocelots and other carnivore species.     

Linking Land‐Use Scenarios,Remote Sensing and Monitoring to Project Impact of Management Decisions

Large‐scale modifications of natural ecosystems lead to mosaics of natural, semi‐natural and intensively used habitats. To improve communication in conservation planning, managers and other stakeholders need spatially explicit projections at the landscape scale of future biodiversity under different land‐use scenarios. For that purpose, we visualized the potential effect of five forest management scenarios on the avifauna of Kakamega Forest, western Kenya using different measures of bird diversity and GIS data. Future projections of bird diversity combined: (1) remotely sensed data on the spatial distribution of different forest management types; (2) field‐based data on the biodiversity of birds in the different management types; and (3) forest management scenarios that took into account possible views of various stakeholder groups. Management scenarios based on the species richness of forest specialists were very informative, because they reflected differences in the proportions of near‐natural forest types among the five scenarios. Projections based on community composition were even more meaningful, as they mirrored not only the proportions of near‐natural forest types, but also their perimeter to area ratios. This highlights that it is important to differentiate effects of the total area of available habitat and the degree of habitat fragmentation, both for species richness and community composition. Furthermore, our study shows that an approach that combines land‐use scenarios, remote sensing and field data on biodiversity can be used to visualize future biodiversity. As such, visualizations of alternative scenarios are valuable for successful communication about conservation planning considering different groups of stakeholders in species‐rich tropical forests.     

Debating Ethics in HIV Research: Gaps between Policy and Practice in Nigeria

HIV prevention is a critical health issue in Nigeria; a country that has one of the worst HIV epidemic profiles in the world. With 270,000 new infections in 2012, Nigeria is a prime site for HIV prevention research. One effect of the HIV epidemic has been to revolutionalise ethical norms for the conduct of research: it is now considered unethical to design and implement HIV related studies without community engagement. Unfortunately, there is very little commensurate effort in building the capacity of local persons to engage actively with researchers, and there is no existing platform to facilitate dialogue between researchers and communities engaged in research in Nigeria. In an effort to address this gap, we undertook a series of three community dialogues (Phase One) and two community‐researcher interface meetings (Phase Two) in Nigeria. This paper aims to give an empirical account of the dialogue from these community engagement processes and provide a resulting critique of the implementation of research ethics practices in Nigeria. It is anticipated that the outputs will: (i) support researchers in designing community‐based research protocols; (ii) inform ethics committees of key considerations during research protocol reviews from a community perspective; and (iii) inform policy makers and research sponsors about issues of primary concern to communities with respect to HIV research.     

Dwarf shrub and grass vegetation resistant to long‐term experimental warming while microarthropod abundance declines on the Falkland Islands

Dwarf shrubs are a dominant plant type across many regions of the Earth and have hence a large impact on carbon and nutrient cycling rates. Climate change impacts on dwarf shrubs have been extensively studied in the Northern Hemisphere, and there appears to be large variability in response between ecosystem types and regions. In the Southern Hemisphere, less data are available despite dwarf shrub vegetation being a dominant feature of southern South America and mountainous regions of the Southern Hemisphere. Here, we present the response of an Empetrum rubrum dwarf shrub and a Poa grass community to 12 years of experimental climate manipulation achieved using open top chambers on the Falkland Islands, a cold temperate island group in the South Atlantic. The dwarf shrub and grass vegetation did not change significantly in cover, biomass or species richness over the 12 years period in response to climate warming scenarios of up to 1°C reflecting annual warming levels predicted in this region for the coming decades. The soil microarthropod community, however, responded with declines in abundance (37%) under warming conditions in the grass community, but no such changes were observed in the dwarf shrub community. Overall, our data indicate that dwarf shrub communities are resistant to the levels of climate warming predicted over the coming decades in the southern South America region and will, therefore, remain a dominant driver of local ecosystem properties.     

The role of community engagement in addressing bystander risks in research: The case of a Zika virus controlled human infection study

There is limited guidance on how to assess the ethical acceptability of research risks that extend beyond research participants to third parties (or “research bystanders”). Community or stakeholder engagement has been proposed as one way to address potential harms to community members, including bystanders. Despite widespread agreement on the importance of community engagement in biomedical research, this umbrella term includes many different goals and approaches, agreement on which is ethically required or recommended for a particular context. We analyse the case of a potential Zika virus human challenge trial to assess whether and how community engagement can help promote the ethical acceptability of research posing risks to bystanders. We conclude that, in addition to having intrinsic value, community engagement can improve the identification of bystander risks, effective approaches to minimizing them, and transparency about bystander risks for host communities.     

ACCESS TO TREATMENT IN HIV PREVENTION TRIALS: PERSPECTIVES FROM A SOUTH AFRICAN COMMUNITY

Access to treatment, in HIV vaccine trials (HVTs), remains ethically controversial. In most prevention trials, including in South Africa, participants who seroconvert are referred to publicly funded programmes for treatment. This strategy is problematic when there is inadequate and uneven access to public sector antiretroviral therapy (ART) and support resources. The responsibilities, if any, of researchers, sponsors and public health authorities involved in HVTs has been hotly debated among academics, scholars, representatives of international organizations and sponsors. However, there is little published on community perceptions. Recent guidance asserts that communities should make inputs into treatment and care decisions. This qualitative study explored a South African community's perceptions of who should provide what to HVT participants as well as how and why this should be done. Twenty‐nine adults working at or attending five primary health care clinics in two rural areas in KwaZulu‐Natal participated in in‐depth interviews. Respondents expressed that researchers should ‘help participants to access’ treatment and care ‘because they are in a position to do so’ and ‘are in a relationship with’ trial participants. Respondents suggested that researchers could help by ‘facilitating referral’ until such time that participants can access care and treatment on their own. We highlight a series of implications for researchers in HVTs, including their need to be aware of prospective participants' considerable trust in and respect for researchers, the responsibility that this places on them, and the need for clear communication with communities so as not to erode community trust.     

Molecular approach to describing a seed‐based food web: the post‐dispersal granivore community of an invasive plant

Communities of post‐dispersal granivores can shape the density and dispersion of exotic plants and invasive weeds, yet plant ecologists have a limited perception of the relative trophic linkages between a seed species and members of its granivore community. Dandelion seeds marked with Rabbit IgG were disseminated into replicated plots in the recipient habitat (South Dakota) and the native range (Czech Republic). Arthropods were collected in pitfall traps, and their guts were searched for the protein marker using enzyme‐linked immunosorbent assay (ELISA). Seed dishes were placed in each plot, and dandelion seed removal rates were measured. The entire experiment was repeated five times over the dandelion flowering period. Gut analysis revealed that approximately 22% of specimens tested positive for the seed marker. A more diverse granivore community had trophic linkages to seeds than has been previously realized under field conditions. This community included taxa such as isopods, millipedes, weevils, rove beetles, and caterpillars, in addition to the traditionally recognized ants, crickets, and carabid beetles. Rarefaction and Chao analysis estimated approximately 16 and 27 species in the granivore communities of the Czech Republic and South Dakota, respectively. Synthesis: Generalist granivore communities are diverse and polyphagous, and are clearly important as a form of biotic resistance to invasive and weedy plants. These granivore communities can be managed to limit population growth of these pests.     

Algal and Fungal Diversity in Antarctic Lichens

The composition of lichen ecosystems except mycobiont and photobiont has not been evaluated intensively. In addition, recent studies to identify algal genotypes have raised questions about the specific relationship between mycobiont and photobiont. In the current study, we analyzed algal and fungal community structures in lichen species from King George Island, Antarctica, by pyrosequencing of eukaryotic large subunit (LSU) and algal internal transcribed spacer (ITS) domains of the nuclear rRNA gene. The sequencing results of LSU and ITS regions indicated that each lichen thallus contained diverse algal species. The major algal operational taxonomic unit (OTU) defined at a 99% similarity cutoff of LSU sequences accounted for 78.7–100% of the total algal community in each sample. In several cases, the major OTUs defined by LSU sequences were represented by two closely related OTUs defined by 98% sequence similarity of ITS domain. The results of LSU sequences indicated that lichen‐associated fungi belonged to the Arthoniomycetes, Eurotiomycetes, Lecanoromycetes, Leotiomycetes, and Sordariomycetes of the Ascomycota, and Tremellomycetes and Cystobasidiomycetes of the Basidiomycota. The composition of major photobiont species and lichen‐associated fungal community were mostly related to the mycobiont species. The contribution of growth forms or substrates on composition of photobiont and lichen‐associated fungi was not evident.     

Plant‐made E2 glycoprotein single‐dose vaccine protects pigs against classical swine fever

Classical Swine Fever Virus (CSFV) causes classical swine fever, a highly contagious hemorrhagic fever affecting both feral and domesticated pigs. Outbreaks of CSF in Europe, Asia, Africa and South America had significant adverse impacts on animal health, food security and the pig industry. The disease is generally contained by prevention of exposure through import restrictions (e.g. banning import of live pigs and pork products), localized vaccination programmes and culling of infected or at‐risk animals, often at very high cost. Current CSFV‐modified live virus vaccines are protective, but do not allow differentiation of infected from vaccinated animals (DIVA), a critical aspect of disease surveillance programmes. Alternatively, first‐generation subunit vaccines using the viral protein E2 allow for use of DIVA diagnostic tests, but are slow to induce a protective response, provide limited prevention of vertical transmission and may fail to block viral shedding. CSFV E2 subunit vaccines from a baculovirus/insect cell system have been developed for several vaccination campaigns in Europe and Asia. However, this expression system is considered expensive for a veterinary vaccine and is not ideal for wide‐spread deployment. To address the issues of scalability, cost of production and immunogenicity, we have employed an Agrobacterium‐mediated transient expression platform in Nicotiana benthamiana and formulated the purified antigen in novel oil‐in‐water emulsion adjuvants. We report the manufacturing of adjuvanted, plant‐made CSFV E2 subunit vaccine. The vaccine provided complete protection in challenged pigs, even after single‐dose vaccination, which was accompanied by strong virus neutralization antibody responses.     

Cadmium‐induced and trans‐generational changes in the cultivable and total seed endophytic community of Arabidopsis thaliana

Trans‐generational adaptation is important to respond rapidly to environmental challenges and increase overall plant fitness. Besides well‐known mechanisms such as epigenetic modifications, vertically transmitted endophytic bacteria might contribute to this process. The cultivable and total endophytic communities of several generations of Arabidopsis thaliana seeds harvested from plants exposed to cadmium (Cd) or not exposed were investigated. The diversity and richness of the seed endophytic community decreased with an increasing number of generations. Aeromicrobium and Pseudonocardia were identified as indicator species in seeds from Cd‐exposed plants, while Rhizobium was abundantly present in both seed types. Remarkably, Rhizobium was the only genus that was consistently detected in seeds of all generations, which suggests that the phenotypic characteristics were more important as selection criteria for which bacteria are transferred to the next plant generation than the actual genera. Production of IAA was an important trait for endophytes from both seed types, while ACC deaminase activity and Cd tolerance were mainly associated with seed endophytes from Cd‐exposed plants. Understanding how different factors influence the seed endophytic community can help us to improve seed quality and plant growth through different biotechnological applications.     

Community dynamics of nematodes after Larsen ice‐shelf collapse in the eastern Antarctic Peninsula

Free‐living marine nematode communities of the Larsen B embayment at the eastern Antarctic Peninsula were investigated to provide insights on their response and colonization rate after large‐scale ice‐shelf collapse. This study compares published data on the post‐collapse situation from 2007 with new material from 2011, focusing on two locations in the embayment that showed highly divergent communities in 2007 and that are characterized by a difference in timing of ice‐shelf breakup. Data from 2007 exposed a more diverse community at outer station B.South, dominated by the genus Microlaimus. On the contrary, station B.West in the inner part of Larsen B was poor in both numbers of individuals and genera, with dominance of a single Halomonhystera species. Re‐assessment of the situation in 2011 showed that communities at both stations diverged even more, due to a drastic increase in Halomonhystera at B.West compared to relatively little change at B.South. On a broader geographical scale, it seems that B.South gradually starts resembling other Antarctic shelf communities, although the absence of the genus Sabatieria and the high abundance of Microlaimus still set it apart nine years after the main Larsen B collapse. In contrast, thriving of Halomonhystera at B.West further separates its community from other Antarctic shelf areas.     

Species‐specific adaptations explain resilience of herbaceous understorey to increased precipitation variability in a Mediterranean oak woodland

To date, the implications of the predicted greater intra‐annual variability and extremes in precipitation on ecosystem functioning have received little attention. This study presents results on leaf‐level physiological responses of five species covering the functional groups grasses, forbs, and legumes in the understorey of a Mediterranean oak woodland, with increasing precipitation variability, without altering total annual precipitation inputs. Although extending the dry period between precipitation events from 3 to 6 weeks led to increased soil moisture deficit, overall treatment effects on photosynthetic performance were not observed in the studied species. This resilience to prolonged water stress was explained by different physiological and morphological strategies to withstand periods below the wilting point, that is, isohydric behavior in Agrostis, Rumex, and Tuberaria, leaf succulence in Rumex, and taproots in Tolpis. In addition, quick recovery upon irrigation events and species‐specific adaptations of water‐use efficiency with longer dry periods and larger precipitation events contributed to the observed resilience in productivity of the annual plant community. Although none of the species exhibited a change in cover with increasing precipitation variability, leaf physiology of the legume Ornithopus exhibited signs of sensitivity to moisture deficit, which may have implications for the agricultural practice of seeding legume‐rich mixtures in Mediterranean grassland‐type systems. This highlights the need for long‐term precipitation manipulation experiments to capture possible directional changes in species composition and seed bank development, which can subsequently affect ecosystem state and functioning.     

HIV Self-Testing Could “Revolutionize Testing in South Africa,but It Has Got to Be Done Properly”: Perceptions of Key Stakeholders

South Africa bears the world’s largest burden of HIV with over 6.4 million people living with the virus. The South African government’s response to HIV has yielded remarkable results in recent years; over 13 million South Africans tested in a 2012 campaign and over 2 million people are on antiretroviral treatment. However, with an HIV & AIDS and STI National Strategic Plan aiming to get 80 percent of the population to know their HIV status by 2016, activists and public health policy makers argue that non-invasive HIV self-testing should be incorporated into the country HIV Counseling and Testing [HCT] portfolios. In-depth qualitative interviews (N = 12) with key stakeholders were conducted from June to July 2013 in South Africa. These included two government officials, four non-governmental stakeholders, two donors, three academic researchers, and one international stakeholder. All stakeholders were involved in HIV prevention and treatment and influenced HCT policy and research in South Africa and beyond. The interviews explored: interest in HIV self-testing; potential distribution channels for HIV self-tests to target groups; perception of requirements for diagnostic technologies that would be most amenable to HIV self-testing and opinions on barriers and opportunities for HIV-linkage to care after receiving positive test results. While there is currently no HIV self-testing policy in South Africa, and several barriers exist, participants in the study expressed enthusiasm and willingness for scale-up and urgent need for further research, planning, establishment of HIV Self-testing policy and programming to complement existing facility-based and community-based HIV testing systems. Introduction of HIV self-testing could have far-reaching positive effects on holistic HIV testing uptake, giving people autonomy to decide which approach they want to use for HIV testing, early diagnosis, treatment and care for HIV particularly among hard-to reach groups, including men.