Epitope mapping and fine specificity of human T and B cell responses for novel candidate blood-stage malaria vaccine P27A

P27A is a novel synthetic malaria vaccine candidate derived from the blood stage Plasmodium falciparum protein Trophozoite Exported Protein 1 (TEX1/PFF0165c). In phase 1a/1b clinical trials in malaria unexposed adults in Switzerland and in malaria pre-exposed adults in Tanzania, P27A formulated with Alhydrogel and GLA-SE adjuvants induced antigen-specific antibodies and T-cell activity. The GLA-SE adjuvant induced significantly stronger humoral responses than the Alhydrogel adjuvant. Groups of pre-exposed and unexposed subjects received identical vaccine formulations, which supported the comparison of the cellular and humoral response to P27A in terms of fine specificity and affinity for populations and adjuvants. Globally, fine specificity of the T and B cell responses exhibited preferred recognized sequences and did not highlight major differences between adjuvants or populations. Affinity of anti-P27A antibodies was around 10−8 M in all groups. Pre-exposed volunteers presented anti-P27A with higher affinity than unexposed volunteers. Increasing the dose of GLA-SE from 2.5 to 5 μg in pre-exposed volunteers improved anti-P27A affinity and decreased the number of recognized epitopes. These results indicate a higher maturation of the humoral response in pre-exposed volunteers, particularly when immunized with P27A formulated with 5 μg GLA-SE

Qualitative cost-benefit analysis of using pesticidal plants in smallholder crop protection

Assessing the potential drivers of farmers using pesticidal plants for crop protection is essential for wider adoption. However, few studies have focused on collaborative assessments of the underlying trade-offs when using pesticidal plant extracts for pest control. Smallholder farmers in northern Tanzania involved in farmer driven research assessing pesticidal plants evaluated the costs, benefits, trade-offs and areas for future investment. A questionnaire was used to collect demographic information from 77 farmers and their views on pest problems and crop protection in common bean production. This was followed by small focus group discussions (n = 9) using a participatory framework to elucidate the costs and benefits of adopting pesticidal plant technology. A multiple correspondence analysis showed that pesticidal plant use was associated with men greater than 50 years old, and synthetic pesticide use was associated with younger aged farmers and women. Farmers who used synthetics generally did not report the presence of common pest species found in common bean production, whereas farmers who used pesticidal plants were associated with more frequent reports of pest species. This participatory cost–benefit analysis highlighted that tools and processing challenges were the main costs to using pesticidal plants. The main benefit reported when using pesticidal plants was a general improvement to family health. Farmers expressed overall a positive outcome when using pesticidal plants for crop protection and recommended that future investments focus on improving access to tools and education regarding plant processing and extraction to improve uptake of the technology by smallholder farmers

The long and challenging road to capitalize on plant-based extracts from the lab to the field.

Negative impacts of chemical pesticide, social demand (healthier food), organic farming organization, rising costs of inputs linked to oil market and their importation (in Africa), and the circular economy approach are a few arguments/opportunities that underlie the roll-out of alternative solutions, including botanicals

Understanding farmer knowledge and site factors in relation to soil-borne pests and pathogens to support agroecological intensification of smallholder bean production systems

Introduction: Pests and diseases limit common bean (Phaseolus vulgaris) production in intensifying smallholder farming systems of sub-Saharan Africa. Soil-borne pests and diseases (SPD) are particularly challenging for farmers to distinguish and manage in cropping systems that vary in terms of soils, farmer knowledge, and management factors. Few studies have examined soil drivers of SPD in smallholder systems, integrated with farmers’ perceptions and management practices. Methods: In Kilimanjaro, Tanzania, we assessed farmer knowledge and SPD management for common bean alongside soil type and soil quality. Focus group discussions and field survey findings including farmer observations and soil nutrient balances were integrated with soil analyses of farmers’ fields. Multiple correspondence analysis (MCA) and principal component analysis (PCA) assessed relationships among farmer demographics, pests and diseases, soil characteristics, and management practices. Results and discussion: Surveys revealed that 100% of farmers knew of the bean foliage beetle (Ootheca bennigseni) but few recognized the soilborne pest Ophiomyia spp. or bean fly despite it being more destructive. About a third of farmers knew of root rot diseases caused by Pythium spp. and Fusarium spp. Synthetic pesticides were used by 72% of farmers to control pests, while about half that (37%) used pesticidal plants, particularly Tephrosia vogelii extracts sprayed on foliage. Regarding SPD, 90% of farmers reported that their management practices were ineffective. Meanwhile, synthetic fertilizers were used by nearly all farmers in beans intercropped with maize (Zea mays), whilst very few farmers used manure or compost. Soil available phosphorus was low but showed a balance between inputs and outputs regardless of whether fields were owned. Field nitrogen balances were more negative when fields were owned by farmers. An MCA showed that older farmers employed a greater number of pest control practices. The PCA showed that field variability was dominated by soil organic matter, elevation, and soil pH. Higher organic matter levels were also associated with less stunting and wilting of beans observed by farmers. Our results suggest that research and farmer learning about SPD ecology are key gaps, alongside recycling of organic residues to soils. Cost-effective and sustainable practices to manage bean SPDs for smallholders are also needed

Population pharmacokinetics of antimalarial naphthoquine in combination with artemisinin in Tanzanian children and adults: dose optimization

The combination antimalarial therapy of artemisinin-naphthoquine (ART-NQ) was developed as a single-dose therapy, aiming to improve adherence relative to the multiday schedules of other artemisinin combination therapies. The pharmacokinetics of ART-NQ has not been well characterized, especially in children. A pharmacokinetic study was conducted in adults and children over 5 years of age (6 to 10, 11 to 17, and >/=18 years of age) with uncomplicated malaria in Tanzania. The median weights for the three age groups were 20, 37.5, and 55 kg, respectively. Twenty-nine patients received single doses of 20 mg/kg of body weight for artemisinin and 8 mg/kg for naphthoquine, and plasma drug concentrations were assessed at 13 time points over 42 days from treatment. We used nonlinear mixed-effects modeling to interpret the data, and allometric scaling was employed to adjust for the effect of body size. The pharmacokinetics of artemisinin was best described by one-compartment model and that of naphthoquine by a two-compartment disposition model. Clearance values for a typical patient (55-kg body weight and 44.3-kg fat-free mass) were estimated as 66.7 L/h (95% confidence interval [CI], 57.3 to 78.5 L/h) for artemisinin and 44.2 L/h (95% CI, 37.9 to 50.6 L/h) for naphthoquine. Nevertheless, we show via simulation that patients weighing >/=70 kg achieve on average a 30% lower day 7 concentration compared to a 48-kg reference patient at the doses tested, suggesting dose increases may be warranted to ensure adequate exposure. (This study has been registered at ClinicalTrials.gov under identifier NCT01930331.)

Analysing and Recommending Options for Maintaining Universal Coverage with Long-Lasting Insecticidal Nets: The Case of Tanzania in 2011.

Tanzania achieved universal coverage with long-lasting insecticidal nets (LLINs) in October 2011, after three years of free mass net distribution campaigns and is now faced with the challenge of maintaining high coverage as nets wear out and the population grows. A process of exploring options for a continuous or "Keep-Up" distribution system was initiated in early 2011. This paper presents for the first time a comprehensive national process to review the major considerations, findings and recommendations for the implementation of a new strategy. Stakeholder meetings and site visits were conducted in five locations in Tanzania to garner stakeholder input on the proposed distribution systems. Coverage levels for LLINs and their decline over time were modelled using NetCALC software, taking realistic net decay rates, current demographic profiles and other relevant parameters into consideration. Costs of the different distribution systems were estimated using local data. LLIN delivery was considered via mass campaigns, Antenatal Care-Expanded Programme on Immunization (ANC/EPI), community-based distribution, schools, the commercial sector and different combinations of the above. Most approaches appeared unlikely to maintain universal coverage when used alone. Mass campaigns, even when combined with a continuation of the Tanzania National Voucher Scheme (TNVS), would produce large temporal fluctuations in coverage levels; over 10 years this strategy would require 63.3 million LLINs and a total cost of $444 million USD. Community mechanisms, while able to deliver the required numbers of LLINs, would require a massive scale-up in monitoring, evaluation and supervision systems to ensure accurate application of identification criteria at the community level. School-based approaches combined with the existing TNVS would reach most Tanzanian households and deliver 65.4 million LLINs over 10 years at a total cost of$449 million USD and ensure continuous coverage. The cost of each strategy was largely driven by the number of LLINs delivered. The most cost-efficient strategy to maintain universal coverage is one that best optimizes the numbers of LLINs needed over time. A school-based approach using vouchers targeting all students in Standards 1, 3, 5, 7 and Forms 1 and 2 in combination with the TNVS appears to meet best the criteria of effectiveness, equity and efficiency

Biological control interventions reduce pest abundance and crop damage while maintaining natural enemies in sub-Saharan Africa: a meta-analysis

Insect pests are a major challenge to smallholder crop production in sub-Saharan Africa (SSA), where access to synthetic pesticides, which are linked to environmental and health risks, is often limited. Biological control interventions could offer a sustainable solution, yet an understanding of their effectiveness is lacking. We used a meta-analysis approach to investigate the effectiveness of commonly used biocontrol interventions and botanical pesticides on pest abundance (PA), crop damage (CD), crop yield (Y) and natural enemy abundance (NEA) when compared with controls with no biocontrol and with synthetic pesticides. We also evaluated whether the magnitude of biocontrol effectiveness was affected by type of biocontrol intervention, crop type, pest taxon, farm type and landscape configuration. Overall, from 99 studies on 31 crops, we found that compared to no biocontrol, biocontrol interventions reduced PA by 63%, CD by over 50% and increased Y by over 60%. Compared to synthetic pesticides, biocontrol resulted in comparable PA and Y, while NEA was 43% greater. Our results also highlighted that the potential for biocontrol to be modulated by landscape configuration is a critical knowledge gap in SSA. We show that biocontrol represents an effective tool for smallholder farmers, which can maintain yields without associated negative pesticide effects. Furthermore, the evidence presented here advocates strongly for including biocontrol practices in national and regional agricultural policies

Extracts of common pesticidal plants increase plant growth and yield in common bean plants

Common bean (Phaseolus vulgaris) is an important food and cash crop in many countries. Bean crop yields in sub-Saharan Africa are on average 50% lower than the global average, which is largely due to severe problems with pests and diseases as well as poor soil fertility exacerbated by low-input smallholder production systems. Recent on-farm research in eastern Africa has shown that commonly available plants with pesticidal properties can successfully manage arthropod pests. However, reducing common bean yield gaps still requires further sustainable solutions to other crop provisioning services such as soil fertility and plant nutrition. Smallholder farmers using pesticidal plants have claimed that the application of pesticidal plant extracts boosts plant growth, potentially through working as a foliar fertiliser. Thus, the aims of the research presented here were to determine whether plant growth and yield could be enhanced and which metabolic processes were induced through the application of plant extracts commonly used for pest control in eastern Africa. Extracts from Tephrosia vogelii and Tithonia diversifolia were prepared at a concentration of 10% w/v and applied to potted bean plants in a pest-free screen house as foliar sprays as well as directly to the soil around bean plants to evaluate their contribution to growth, yield and potential changes in primary or secondary metabolites. Outcomes of this study showed that the plant extracts significantly increased chlorophyll content, the number of pods per plant and overall seed yield. Other increases in metabolites were observed, including of rutin, phenylalanine and tryptophan. The plant extracts had a similar effect to a commercially available foliar fertiliser whilst the application as a foliar spray was better than applying the extract to the soil. These results suggest that pesticidal plant extracts can help overcome multiple limitations in crop provisioning services, enhancing plant nutrition in addition to their established uses for crop pest management

Phytochemical analysis of Tephrosia vogelii across East Africa reveals three chemotypes that influence its use as a pesticidal plant

Tephrosia vogelii is a plant species chemically characterized by the presence of entomotoxic rotenoids and used widely across Africa as a botanical pesticide. Phytochemical analysis was conducted to establish the presence and abundance of the bioactive principles in this species across three countries in East Africa: Tanzania, Kenya, and Malawi. Analysis of methanolic extracts of foliar parts of T. vogelii revealed the occurrence of two distinct chemotypes that were separated by the presence of rotenoids in one, and flavanones and flavones that are not bioactive against insects on the other. Specifically, chemotype 1 contained deguelin as the major rotenoid along with tephrosin, and rotenone as a minor component, while these compounds were absent from chemotype 2, which contained previously reported flavanones and flavones including obovatin‐3‐O‐methylether. Chemotype 3 contained a combination of the chemical profiles of both chemotype 1 and 2 suggesting a chemical hybrid. Plant samples identified as chemotype 1 showed chemical consistency across seasons and altitudes, except in the wet season where a significant difference was observed for samples in Tanzania. Since farmers are unable to determine the chemical content of material available care must be taken in promoting this species for pest management without first establishing efficacy. While phytochemical analysis serves as an important tool for quality control of pesticidal plants, where analytical facilities are not available simple bioassays could be developed to enable extension staff and farmers to determine the efficacy of their plants and ensure only effective materials are adopted

The adjuvant GLA-SE promotes human Tfh cell expansion and emergence of public TCRβ clonotypes

The generation of protective humoral immunity after vaccination relies on the productive interaction between antigen-specific B cells and T follicular helper (Tfh) cells. Despite the central role of Tfh cells in vaccine responses, there is currently no validated way to enhance their differentiation in humans. From paired human lymph node and blood samples, we identify a population of circulating Tfh cells that are transcriptionally and clonally similar to germinal center Tfh cells. In a clinical trial of vaccine formulations, circulating Tfh cells were expanded in Tanzanian volunteers when an experimental malaria vaccine was adjuvanted in GLA-SE but not when formulated in Alum. The GLA-SE–formulated peptide was associated with an increase in the extrafollicular antibody response, long-lived antibody production, and the emergence of public TCRβ clonotypes in circulating Tfh cells. We demonstrate that altering vaccine adjuvants is a rational approach for enhancing Tfh cells in humans, thereby supporting the long-lived humoral immunity that is required for effective vaccines.</jats:p