Think global, act local: using a translocal approach to understand community-based organisations' responses to planetary health crises during COVID-19.

Little is known on how community-based responses to planetary health crises, such as the COVID-19 pandemic, can integrate concerns about livelihoods, equity, health, wellbeing, and the environment. We used a translocal learning approach to co-develop insights on community-based responses to complex health and environmental and economic crises with leaders from five organisations working with communities at the front line of intersecting planetary health challenges in Finland, India, Kenya, Peru, and the USA. Translocal learning supports collective knowledge production across different localities in ways that value local perspectives but transcend national boundaries. There were three main findings from the translocal learning process. First, thanks to their proximity to the communities they served, community-based organisations (CBOs) can quickly identify the ways in which COVID-19 might worsen existing social and health inequities. Second, localised CBO actions are key to supporting communities with unique challenges in the face of systemic planetary health crises. Third, CBOs can develop rights-based, ecologically-minded actions responding to local priorities and mobilising available resources. Our findings show how solutions to planetary health might come from small-scale community initiatives that are well connected within and across contexts. Locally-focused globally-aware actions should be harnessed through greater recognition, funding, and networking opportunities. Globally, planetary health initiatives should be supported by applying the principles of subsidiarity and translocalism.

A scoping review on women's sexual health in the postpartum period: opportunities for research and practice within low-and middle-income countries.

BACKGROUND: Women's sexual health is generally defined and explored solely in relation to reproductive capacity, and often omits elements of sexual function and/or dysfunction. Concerted focus is given to women's health during pregnancy; however, women's sexual health is largely neglected after childbirth. This scoping review explored how the sexual health of postpartum women has been defined, measured, and researched in low- and middle-income countries (LMICs). METHODS: Articles eligible for review were those that investigated women's sexual health during the first 12 months postpartum and were conducted among women aged 15-49 in LMICs. Eligibility was further restricted to studies that were published within the last 20 years (2001-2021). The initial PubMed search identified 812 articles, but upon further eligibility review, 97 remained. At this time, the decision was made to focus this review only on articles addressing sexual function and/or dysfunction, which yielded 46 articles. Key article characteristics were described and analyzed by outcome. RESULTS: Of the final included articles, five studies focused on positive sexual health, 13 on negative sexual health, and the remaining 28 on both positive and negative sexual health or without specified directionality. The most common outcome examined was resumption of sex after childbirth. Most studies occurred within sub-Saharan Africa (n = 27), with geographic spread throughout the Middle East (n = 10), Asia (n = 5), North Africa (n = 3), and cross-geography (n = 1); notably, all five studies on positive sexual health were conducted in Iran. Negative sexual health outcomes included vaginismus, dyspareunia, episiotomy, perineal tears, prolapse, infection, obstetric fistula, female genital cutting, postnatal pain, uterine prolapse, coercion to resume sex, sexual violence, and loss of sexual desire/arousal. Most studies were quantitative, though eight qualitative studies elucidated the difficulties women endured in receiving information specific to sexual health and hesitance in seeking help for sexual morbidities in the postpartum period. CONCLUSIONS: Overall, the evidence base surrounding women's sexual health in the postpartum period within LMICs remains limited, with most studies focusing solely on the timing of resumption of sex. Integration of sexual health counseling into postnatal care and nonjudgmental service provision can help women navigate these bodily changes and ultimately improve their sexual health.

The nutritional care of people living with dementia at home: A scoping review.

There are an increasing number of people with dementia living in their own home for longer, often supported by a family member. The symptoms of dementia can affect an individual's nutritional status, which can lead to a reduced quality of life for the person with dementia and their family members. A scoping review was conducted from July 2016 until September 2016, using a recognised framework, to explore what is currently known, and identify any gaps in the research regarding the nutritional care of people living with dementia at home. This included any interventions that may have been trialled or implemented, and the views of those living with dementia, carers and clinicians. Six electronic databases were searched from inception to July 2016. A review team was involved in screening and data extraction for selected articles. Published qualitative and quantitative studies were included that explored the nutritional care of people living with dementia at home. Methods included data extraction and conventional content analysis. Stakeholders were involved in the development of final categories. Following screening, 61 studies reported in 63 articles were included. Most studies were cross-sectional (n = 24), cohort (n = 15) or qualitative (n = 9). Only three were randomised controlled trials. Three overarching categories represented the results: Timely identification of nutritional risk and subsequent regular monitoring of nutritional status, multi-component tailored interventions and the influence of the care-giving dyad on nutritional status. Many studies identify people living at home with dementia as a vulnerable group prone to malnutrition; however, a lack of interventions exists to address the increased risk. There is a lack of research exploring the role of home care providers and healthcare professionals in the provision of nutritional care. Further research is required to explore how the emotional aspect of the care-giving dyad influences nutritional care.

'Snack' versus 'meal': The impact of label and place on food intake.

Eating behaviour is influenced by both cognitions and triggers in the environment. The potential difference between a 'snack' and a 'meal' illustrates these factors and the way in which they interact, particularly in terms of the label used to describe food and the way it is presented. To date no research has specifically explored the independent and combined impact of label and presentation on eating behaviour. Using a preload/taste test design this experimental study evaluated the impact of label ('snack' vs. 'meal') and place ('snack' vs. 'meal') of a preload on changes in desire to eat and subsequent food intake. Eighty female participants consumed a pasta preload which labelled as either a 'snack' or a 'meal' and presented as either a 'snack' (standing and eating from a container) or a 'meal' (eating at a table from a plate), generating four conditions. The results showed main effects of label and place with participants consuming significantly more sweet mass (specifically chocolate) at the taste test when the preload had been labelled a 'snack' and more total mass and calories when the preload had been presented as a 'snack'. No label by place interactions were found. The results also showed a combined effect of both label and place with those who had eaten the preload both labelled and presented as a 'snack' consuming significantly more in terms of nearly all measures of food intake than those in the other conditions. To conclude, label and presentation influence subsequent food intake both independently and combined which is pertinent given the increase in 'snacking' in contemporary culture.

DNA prime/Adenovirus boost malaria vaccine encoding P. falciparum CSP and AMA1 induces sterile protection associated with cell-mediated immunity.

BACKGROUND: Gene-based vaccination using prime/boost regimens protects animals and humans against malaria, inducing cell-mediated responses that in animal models target liver stage malaria parasites. We tested a DNA prime/adenovirus boost malaria vaccine in a Phase 1 clinical trial with controlled human malaria infection. METHODOLOGY/PRINCIPAL FINDINGS: The vaccine regimen was three monthly doses of two DNA plasmids (DNA) followed four months later by a single boost with two non-replicating human serotype 5 adenovirus vectors (Ad). The constructs encoded genes expressing P. falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). The regimen was safe and well-tolerated, with mostly mild adverse events that occurred at the site of injection. Only one AE (diarrhea), possibly related to immunization, was severe (Grade 3), preventing daily activities. Four weeks after the Ad boost, 15 study subjects were challenged with P. falciparum sporozoites by mosquito bite, and four (27%) were sterilely protected. Antibody responses by ELISA rose after Ad boost but were low (CSP geometric mean titer 210, range 44-817; AMA1 geometric mean micrograms/milliliter 11.9, range 1.5-102) and were not associated with protection. Ex vivo IFN-γ ELISpot responses after Ad boost were modest (CSP geometric mean spot forming cells/million peripheral blood mononuclear cells 86, range 13-408; AMA1 348, range 88-1270) and were highest in three protected subjects. ELISpot responses to AMA1 were significantly associated with protection (p = 0.019). Flow cytometry identified predominant IFN-γ mono-secreting CD8+ T cell responses in three protected subjects. No subjects with high pre-existing anti-Ad5 neutralizing antibodies were protected but the association was not statistically significant. SIGNIFICANCE: The DNA/Ad regimen provided the highest sterile immunity achieved against malaria following immunization with a gene-based subunit vaccine (27%). Protection was associated with cell-mediated immunity to AMA1, with CSP probably contributing. Substituting a low seroprevalence vector for Ad5 and supplementing CSP/AMA1 with additional antigens may improve protection. TRIAL REGISTRATION: ClinicalTrials.govNCT00870987.

Adenovirus 5-vectored P. falciparum vaccine expressing CSP and AMA1. Part A: safety and immunogenicity in seronegative adults.

BACKGROUND: Models of immunity to malaria indicate the importance of CD8+ T cell responses for targeting intrahepatic stages and antibodies for targeting sporozoite and blood stages. We designed a multistage adenovirus 5 (Ad5)-vectored Plasmodium falciparum malaria vaccine, aiming to induce both types of responses in humans, that was tested for safety and immunogenicity in a Phase 1 dose escalation trial in Ad5-seronegative volunteers. METHODOLOGY/PRINCIPAL FINDINGS: The NMRC-M3V-Ad-PfCA vaccine combines two adenovectors encoding circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). Group 1 (n = 6) healthy volunteers received one intramuscular injection of 2×10∧10 particle units (1×10∧10 each construct) and Group 2 (n = 6) a five-fold higher dose. Transient, mild to moderate adverse events were more pronounced with the higher dose. ELISpot responses to CSP and AMA1 peaked at 1 month, were higher in the low dose (geomean CSP = 422, AMA1 = 862 spot forming cells/million) than in the high dose (CSP = 154, p = 0.049, AMA1 = 423, p = 0.045) group and were still positive at 12 months in a number of volunteers. ELISpot depletion assays identified dependence on CD4+ or on both CD4+ and CD8+ T cells, with few responses dependent only on CD8+ T cells. Intracellular cytokine staining detected stronger CD8+ than CD4+ T cell IFN-γ responses (CSP p = 0.0001, AMA1 p = 0.003), but similar frequencies of multifunctional CD4+ and CD8+ T cells secreting two or more of IFN-γ, TNF-α or IL-2. Median fluorescence intensities were 7-10 fold higher in triple than single secreting cells. Antibody responses were low but trended higher in the high dose group and did not inhibit growth of cultured P. falciparum blood stage parasites. SIGNIFICANCE: As found in other trials, adenovectored vaccines appeared safe and well-tolerated at doses up to 1×10∧11 particle units. This is the first demonstration in humans of a malaria vaccine eliciting strong CD8+ T cell IFN-γ responses. TRIAL REGISTRATION: ClinicalTrials.govNCT00392015.

Adenovirus-5-vectored P. falciparum vaccine expressing CSP and AMA1. Part B: safety, immunogenicity and protective efficacy of the CSP component.

BACKGROUND: A protective malaria vaccine will likely need to elicit both cell-mediated and antibody responses. As adenovirus vaccine vectors induce both these responses in humans, a Phase 1/2a clinical trial was conducted to evaluate the efficacy of an adenovirus serotype 5-vectored malaria vaccine against sporozoite challenge. METHODOLOGY/PRINCIPAL FINDINGS: NMRC-MV-Ad-PfC is an adenovirus vector encoding the Plasmodium falciparum 3D7 circumsporozoite protein (CSP). It is one component of a two-component vaccine NMRC-M3V-Ad-PfCA consisting of one adenovector encoding CSP and one encoding apical membrane antigen-1 (AMA1) that was evaluated for safety and immunogenicity in an earlier study (see companion paper, Sedegah et al). Fourteen Ad5 seropositive or negative adults received two doses of NMRC-MV-Ad-PfC sixteen weeks apart, at 1 x 1010 particle units per dose. The vaccine was safe and well tolerated. All volunteers developed positive ELISpot responses by 28 days after the first immunization (geometric mean 272 spot forming cells/million[sfc/m]) that declined during the following 16 weeks and increased after the second dose to levels that in most cases were less than the initial peak (geometric mean 119 sfc/m). CD8+ predominated over CD4+ responses, as in the first clinical trial. Antibody responses were poor and like ELISpot responses increased after the second immunization but did not exceed the initial peak. Pre-existing neutralizing antibodies (NAb) to Ad5 did not affect the immunogenicity of the first dose, but the fold increase in NAb induced by the first dose was significantly associated with poorer antibody responses after the second dose, while ELISpot responses remained unaffected. When challenged by the bite of P. falciparum-infected mosquitoes, two of 11 volunteers showed a delay in the time to patency compared to infectivity controls, but no volunteers were sterilely protected. SIGNIFICANCE: The NMRC-MV-Ad-PfC vaccine expressing CSP was safe and well tolerated given as two doses, but did not provide sterile protection. TRIAL REGISTRATION: ClinicalTrials.gov NCT00392015.

Process development for the production of an E. coli produced clinical grade recombinant malaria vaccine for Plasmodium vivax.

The global eradication of malaria will require the development of vaccines to prevent infection cause by Plasmodium vivax in addition to Plasmodium falciparum. In an attempt to contribute to this effort we have previously reported the cloning and expression of a vaccine based on the circumsporozoite protein of P. vivax. The synthetic vaccine encodes for a full-length molecule encompassing the N-terminal and C-terminal regions flanking a chimeric repeat region representing VK210 and VK247, the two major alleles of P. vivax CSP. The vaccine, designated vivax malaria protein 001 (VMP001), was purified to >95% homogeneity using a three-column purification scheme and had low endotoxin levels and passed the rabbit pyrogenicity assay. The protein is recognized by monoclonal antibodies directed against the two repeat motifs, as well as polyclonal antibodies. Immunization with VMP001 induced high titer antibodies in mice using Montanide ISA 720. We currently have more than 10,000 doses of purified bulk and 1800 vials of formulated bulk vaccine available for clinical testing and VMP001 is currently undergoing further development as a candidate vaccine to prevent malaria in humans.