Sanitation financing: lessons learnt from application of different financing instruments in Busia county, Kenya

Financial Inclusion Improves Sanitation and Health in Kenya is a Dutch-Government funded project implemented in Busia and Kilifi Counties. The project is founded on a Public-Private Partnership arrangement to create an enabling environment for market-driven approach for scaling up sanitation. The intervention combines demand generation and private sector involvement in developing and delivering sanitation products and services to underserved rural communities. The mainstay strategy applied was Community Led Total sanitation plus (CLTS+) approach. The plus entails financial inclusion targeting communities without sanitation facilities through financial literacy and micro-lending for sanitation improvement. As part of supply side development, Small and Medium Enterprises (SMEs) in sanitation business having also been financially included to strengthen their capacity to respond to thus generated demand. A combination of expanded markets coupled with demand generation has contributed to access to improved sanitation, promising health and livelihood improvements

Controlled human malaria infection (CHMI) outcomes in Kenyan adults is associated with prior history of malaria exposure and anti-schizont antibody response

BACKGROUND: Individuals living in endemic areas acquire immunity to malaria following repeated parasite exposure. We sought to assess the controlled human malaria infection (CHMI) model as a means of studying naturally acquired immunity in Kenyan adults with varying malaria exposure. METHODS: We analysed data from 142 Kenyan adults from three locations representing distinct areas of malaria endemicity (Ahero, Kilifi North and Kilifi South) enrolled in a CHMI study with Plasmodium falciparum sporozoites NF54 strain (Sanaria® PfSPZ Challenge). To identify the in vivo outcomes that most closely reflected naturally acquired immunity, parameters based on qPCR measurements were compared with anti-schizont antibody levels and residence as proxy markers of naturally acquired immunity. RESULTS: Time to endpoint correlated more closely with anti-schizont antibodies and location of residence than other parasite parameters such as growth rate or mean parasite density. Compared to observational field-based studies in children where 0.8% of the variability in malaria outcome was observed to be explained by anti-schizont antibodies, in the CHMI model the dichotomized anti-schizont antibodies explained 17% of the variability. CONCLUSIONS: The CHMI model is highly effective in studying markers of naturally acquired immunity to malaria. Trial registration Clinicaltrials.gov number NCT02739763. Registered 15 April 2016

Insilico Functional Analysis of Genome-Wide Dataset From 17,000 Individuals Identifies Candidate Malaria Resistance Genes Enriched in Malaria Pathogenic Pathways

Recent genome-wide association studies (GWASs) of severe malaria have identified several association variants. However, much about the underlying biological functions are yet to be discovered. Here, we systematically predicted plausible candidate genes and pathways from functional analysis of severe malaria resistance GWAS summary statistics (N = 17,000) meta-analysed across 11 populations in malaria endemic regions. We applied positional mapping, expression quantitative trait locus (eQTL), chromatin interaction mapping, and gene-based association analyses to identify candidate severe malaria resistance genes. We further applied rare variant analysis to raw GWAS datasets (N = 11,000) of three malaria endemic populations including Kenya, Malawi, and Gambia and performed various population genetic structures of the identified genes in the three populations and global populations. We performed network and pathway analyses to investigate their shared biological functions. Our functional mapping analysis identified 57 genes located in the known malaria genomic loci, while our gene-based GWAS analysis identified additional 125 genes across the genome. The identified genes were significantly enriched in malaria pathogenic pathways including multiple overlapping pathways in erythrocyte-related functions, blood coagulations, ion channels, adhesion molecules, membrane signalling elements, and neuronal systems. Our population genetic analysis revealed that the minor allele frequencies (MAF) of the single nucleotide polymorphisms (SNPs) residing in the identified genes are generally higher in the three malaria endemic populations compared to global populations. Overall, our results suggest that severe malaria resistance trait is attributed to multiple genes, highlighting the possibility of harnessing new malaria therapeutics that can simultaneously target multiple malaria protective host molecular pathways

Controlled Human Malaria Infection in Semi-Immune Kenyan Adults (CHMI-SIKA): a study protocol to investigate in vivo Plasmodium falciparum malaria parasite growth in the context of pre-existing immunity [version 2; peer review: 2 approved]

Malaria remains a major public health burden despite approval for implementation of a partially effective pre-erythrocytic malaria vaccine. There is an urgent need to accelerate development of a more effective multi-stage vaccine. Adults in malaria endemic areas may have substantial immunity provided by responses to the blood stages of malaria parasites, but field trials conducted on several blood-stage vaccines have not shown high levels of efficacy. We will use the controlled human malaria infection (CHMI) models with malaria-exposed volunteers to identify correlations between immune responses and parasite growth rates in vivo. Immune responses more strongly associated with control of parasite growth should be prioritized to accelerate malaria vaccine development. We aim to recruit up to 200 healthy adult volunteers from areas of differing malaria transmission in Kenya, and after confirming their health status through clinical examination and routine haematology and biochemistry, we will comprehensively characterize immunity to malaria using >100 blood-stage antigens. We will administer 3,200 aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (PfSPZ Challenge) by direct venous inoculation. Serial quantitative polymerase chain reaction to measure parasite growth rate in vivo will be undertaken. Clinical and laboratory monitoring will be undertaken to ensure volunteer safety. In addition, we will also explore the perceptions and experiences of volunteers and other stakeholders in participating in a malaria volunteer infection study. Serum, plasma, peripheral blood mononuclear cells and whole blood will be stored to allow a comprehensive assessment of adaptive and innate host immunity. We will use CHMI in semi-immune adult volunteers to relate parasite growth outcomes with antibody responses and other markers of host immunity. / Registration: ClinicalTrials.gov identifier NCT02739763

Dual Electron Spectrometer for Magnetospheric Multiscale Mission: Results of the Comprehensive Tests of the Engineering Test Unit

The Magnetospheric Multiscale mission (MMS) is designed to study fundamental phenomena in space plasma physics such as a magnetic reconnection. The mission consists of four spacecraft, equipped with identical scientific payloads, allowing for the first measurements of fast dynamics in the critical electron diffusion region where magnetic reconnection occurs and charged particles are demagnetized. The MMS orbit is optimized to ensure the spacecraft spend extended periods of time in locations where reconnection is known to occur: at the dayside magnetopause and in the magnetotail. In order to resolve fine structures of the three dimensional electron distributions in the diffusion region (reconnection site), the Fast Plasma Investigation's (FPI) Dual Electron Spectrometer (DES) is designed to measure three dimensional electron velocity distributions with an extremely high time resolution of 30 ms. In order to achieve this unprecedented sampling rate, four dual spectrometers, each sampling 180 x 45 degree sections of the sky, are installed on each spacecraft. We present results of the comprehensive tests performed on the DES Engineering & Test Unit (ETU). This includes main parameters of the spectrometer such as energy resolution, angular acceptance, and geometric factor along with their variations over the 16 pixels spanning the 180-degree tophat Electro Static Analyzer (ESA) field of view and over the energy of the test beam. A newly developed method for precisely defining the operational space of the instrument is presented as well. This allows optimization of the trade-off between pixel to pixel crosstalk and uniformity of the main spectrometer parameters

Controlled human malaria infection (CHMI) outcomes in Kenyan adults is associated with prior history of malaria exposure and anti-schizont antibody response

Background Individuals living in endemic areas acquire immunity to malaria following repeated parasite exposure. We sought to assess the controlled human malaria infection (CHMI) model as a means of studying naturally acquired immunity in Kenyan adults with varying malaria exposure. Methods We analysed data from 142 Kenyan adults from three locations representing distinct areas of malaria endemicity (Ahero, Kilifi North and Kilifi South) enrolled in a CHMI study with Plasmodium falciparum sporozoites NF54 strain (Sanaria® PfSPZ Challenge). To identify the in vivo outcomes that most closely reflected naturally acquired immunity, parameters based on qPCR measurements were compared with anti-schizont antibody levels and residence as proxy markers of naturally acquired immunity. Results Time to endpoint correlated more closely with anti-schizont antibodies and location of residence than other parasite parameters such as growth rate or mean parasite density. Compared to observational field-based studies in children where 0.8% of the variability in malaria outcome was observed to be explained by anti-schizont antibodies, in the CHMI model the dichotomized anti-schizont antibodies explained 17% of the variability. Conclusions The CHMI model is highly effective in studying markers of naturally acquired immunity to malaria. Trial registration Clinicaltrials.gov number NCT02739763. Registered 15 April 201

How effective are MPAs? Predation control and 'spill-in effects' in seagrass-coral reef lagoons under contrasting fishery management

Marine protected areas (MPAs) are heavily promoted as a panacea for marine conservation, but lagging and sometimes idiosyncratic protection effects bring their overall effectiveness into question. In Kenyan lagoons, seagrass overgrazing by the sea urchin Tripneustes gratilla has been linked to removal of predators, but overgrazing has also been observed within well-protected MPAs. In this study we investigated the effectiveness of Kenyan MPAs in facilitating predation control over sea urchins, particularly T gratilla, in relation to system (seagrass or coral reef), distance to reefs, and seagrass presence. A strong protection effect on urchin densities on reefs and a negative correlation between T gratilla density and predation pressure (from sea stars, fish and gastropods) in seagrass beds (r(2) = 0.345) confirmed the importance of top-down control. Yet there were no clear effects of protection or distance to reefs in seagrass beds, most likely due to (1) low predator densities in the recently established Mombasa MPA; (2) 'spill-in' of aggregated T gratilla into the older Watamu MPA (potentially facilitated by low predation pressure on the large urchins and nutrient enrichment); and (3) a potential buffering effect of seagrass canopies on predation, regardless of distance to reefs. Effects of seagrass presence differed between areas, but indicated that overgrazing in some areas could be self-regulated by inducing higher urchin mortality. As MPA effects appear to be system-, time- and site-specific, managers should also assess other more holistic approaches (e.g. banned fishing of urchin predators and reduced nutrient input from land runoff) to protect seagrasses

Insight on Fruit Fly IPM Technology Uptake and Barriers to Scaling in Africa

Tephritid fruit flies are considered one of the world’s most notorious pests of horticultural crops, causing extensive direct and indirect damage. Over the past two decades, a comprehensive, integrated pest management (IPM) package for the management of a plethora of fruit fly pests, including Bactrocera dorsalis, B. latifrons, B. zonata, Ceratitis cosyra, C. rosa, C. fasciventris, C. quilici, C. capitata, Dacus spp. and Zeugodacus cucurbitae, has been developed, disseminated and promoted among horticultural growers in Africa. To estimate the numbers of beneficiaries reached by the fruit fly IPM technology and the barriers to technology uptake, we interviewed 290 experts in 30 African countries covering five regions of the continent, and the responses collected were represented as follows: Southern Africa (39.1%), Eastern Africa (31.6%), Western Africa (18.0%), Central Africa (9.0%) and Northern Africa (2.0%). Our results revealed that the use of fruit fly IPM technologies varied across the regions, with Eastern Africa and Western Africa the leading regions, with the highest IPM technology penetration. Field sanitation remains the most common practice for managing fruit flies, followed by protein bait spray, use of biopesticides, male annihilation technique and parasitoid releases. According to the survey, over 101 million people have benefited from the fruit fly IPM interventions in the countries surveyed representing only 19.1% of the estimated beneficiaries. The region that benefitted the most was Eastern Africa (50.2 million), followed by Central and Western Africa (11.7 to 17.7 million), and Southern and Northern Africa had the fewest beneficiaries (10.4 to 11.0 million). The limitations to the IPM technologies uptake varied among the regions, but the common ones include a lack of awareness of the IPM technologies, a lack of access to the IPM products, insufficient training, a low involvement of private sectors and a lack of policies for the regulation of IPM technologies. Although significant strides have been made in promoting the fruit fly IPM technologies over the past two decades, our study reveals that the demand surpasses the current supply. Our study recommends a comprehensive strategy for the dissemination and promotion of the technologies through a multi-institutional alliance that enhances public and private partnerships, digital platforms and youth engagement to consolidate previous gains at the regional and continental levels

Effectiveness of Quadruple Fortified Salt Compared to Double and Single Fortified Salts in Improving Haemoglobin Levels Among Moderately Anemic Women Aged 18–49 Years in Rural Low Resource Setting: Randomized Clinical Trial

Paschal Mdoe,1 Venkatesh Mannar,2 Museveni Justine,1 Godfrey Guga,1 Rose Gadiye,1 Vincent Assey,3 Caroline Kimathi,1 Fatma Abdallah,3 John Paschal,1 Estomih Mduma,1 Levente Diosady2 1Department of Obstetrics and Gynecology, Haydom Lutheran Hospital, Manyara, Tanzania; 2Department of Food Engineering, University of Toronto, Toronto, ON, Canada; 3Department of Food and Nutrition, Tanzania Food and Nutrition Center, Dar Es Salaam, TanzaniaCorrespondence: Paschal Mdoe, P.O. Box 9000, Manyara, Tanzania, Tel +255754429346, Email [email protected]: Micronutrients (iron, iodine, vitamin B12 and folate) deficiency is prevalent globally affecting more than two billion people majority being from low- and middle-income countries. Women of reproductive age are in an increased risk of iron deficiency. About 29.4% of women aged 15– 49 years worldwide are estimated to be affected by iron deficiency. Food fortification with micronutrients is important in addressing micronutrients deficiency.Aim: To evaluate if the quadruple fortified with iodine, iron, vitamin B12, and folic acid (QFS), will be more effective in improving the hemoglobin level of women aged 18 to 49 years compared to the double fortified with iodine and iron (DFS) and iodized salt in rural Tanzania.Methods: A double-blinded three-arm randomized controlled trial was conducted between July 2020 and December 2021 at the Haydom Lutheran Hospital catchment area. We randomized women aged 18– 49 years with haemoglobin between 8 and 12 g/dl who were neither pregnant nor lactating into three groups 55 Iodized salts (IS), 57 Double fortified salt (DFS), and 57 quadruple fortified salt (QFS). The participants used study salt for 10 months.Results: Over the ten months of use of study salts, the overall mean haemoglobin level of women was significantly higher in QFS by 0.43g/dl compared to IS. The ferritin levels were significantly higher in QFS and DFS by 9.60ng/mL and 9.09ng/mL, respectively, compared to IS. Vitamin B12 was insignificantly higher in QFS by 52.19pg/mL compared to DFS, and folate concentration were insignificantly higher in QFS by 7.57nmoL/L and 4.51nmoL/L compared to DFS and IS groups, respectively.Conclusion: Salt fortification with iron, iodine, folate, and Vitamin B12 is feasible and has the potential to increase the serum ferritin, Vitamin B12 and folate levels with subsequent improvement of haemoglobin levels of individuals with relatively low haemoglobin.ClinicalTrial.org Number: NCT04404751.Keywords: iron-deficiency anemia, iodine, iron, vitamin B12, folat

protGear: A protein microarray data pre-processing suite

Protein microarrays are versatile tools for high throughput study of the human proteome, but systematic and non-systematic sources of bias constrain optimal interpretation and the ultimate utility of the data. Published guidelines to limit technical variability whilst maintaining important biological variation favour DNA-based microarrays that often differ fundamentally in their experimental design. Rigorous tools to guide background correction, the quantification of within-sample variation, normalisation, and batch correction specifically for protein microarrays are limited, require extensive investigation and are not centrally accessible. Here, we develop a generic one-stop-shop pre-processing suite for protein microarrays that is compatible with data from the major protein microarray scanners. Our graphical and tabular interfaces facilitate a detailed inspection of data and are coupled with supporting guidelines that enable users to select the most appropriate algorithms to systematically address bias arising in customized experiments. The localization and distribution of background signal intensities determine the optimal correction strategy. A novel function overcomes the limitations in the interpretation of the coefficient of variation when signal intensities are at the lower end of the detection threshold. We demonstrate essential considerations in the experimental design and their impact on a range of algorithms for normalization and minimization of batch effects. Our user-friendly interactive web-based platform eliminates the need for prowess in programming. The open-source R interface includes illustrative examples, generates an auditable record, enables reproducibility, and can incorporate additional custom scripts through its online repository. This versatility will enhance its broad uptake in the infectious disease and vaccine development community