Protecting hope: Situation analysis of vulnerable children in Uganda 2009

The Government of Uganda has focused attention on the problem of orphaned and other vulnerable children through a number of policies, regulations, and initiatives. In 2004, the Ministry of Gender Labor and Social Development developed the National OVC Policy, aimed at improving the quality of life for poor and vulnerable children, such as children who have been orphaned, children who are living on the streets, children who are at risk of abuse, and children exposed to situations of armed conflict. However, despite the many efforts to improve the circumstances of vulnerable children in Uganda, policymakers, donors, and program managers still lack comprehensive and up-to-date information about their numbers, geographic distribution, characteristics, and needs. Furthermore, documentation of existing programs addressing the circumstances of vulnerable children is limited. To address these needs, the United States Agency for International Development (USAID)/Uganda contracted the Population Council and its partners, Uganda Bureau of Statistics and Mathematica Policy Research, to conduct a situation analysis of vulnerable children in Uganda. The situation analysis aims to increase the understanding of the scope of the problem of vulnerable children and the response to it, including the full spectrum of core services, in order to facilitate country-wide planning and to inform current and future programming efforts

PEPFAR special initiative on sexual and gender-based violence: Baseline report

The PEPFAR Special Initiative on Sexual and Gender-Based Violence aims to strengthen services for survivors of sexual violence (SV) though the implementation of a comprehensive model of care in participating PEPFAR partner facilities. This baseline report examines project sites in Uganda and Rwanda and suggests strengthening health services involving training, community and provider awareness and attitudes

Cost-Effective PCR-Based Identification of Tunga penetrans (Siphonaptera) Larvae Extracted from Soil Samples Containing PCR Inhibitor-Rich Material

Tungiasis is a neglected tropical disease caused by skin-penetrating female Tunga penetrans fleas. Although tungiasis causes severe health problems, its ecology is poorly understood and morphological descriptions of the larvae are unavailable. To identify T. penetrans immature stages and sites where they develop, diagnostic PCRs are required. However, flea larvae feed on soil organic matter rich in PCR inhibitors. Here, three DNA preparation methods, including a soil DNA kit that removes inhibitors, a simple ammonium acetate precipitation approach (AmAcet) and a crude lysate of larvae (CL), were combined with amplification by the highly processive FIREPol® Taq or the inhibitor-resistant Phusion® polymerase. Independent of the polymerase used, the frequency of successful amplification, Cq values and PCR efficacies for the low-cost CL and AmAcet methods were superior to the commercial kit for amplification of a 278 bp partial internal transcribed spacer-2 (ITS-2) and a 730 bp pan-Siphonaptera cytochrome oxidase II PCR. For the CL method combined with Phusion® polymerase, the costs were approximately 20-fold lower than for the methods based on the soil DNA kit, which is a considerable advantage in resource-poor settings. The ITS-2 PCR did not amplify Ctenocephalides felis genomic or Tunga trimammilata ITS-2 plasmid DNA, meaning it can be used to specifically identify T. penetrans

Immunoglobulin κ Chain Allotypes (KM) in Onchocerciasis

GM and KM allotypes, powerful tools for genetic characterization of human populations, have been shown to play an important role in genetic predisposition to some infectious diseases. Two diverse racial groups-Afro-Ecuadorians and Amerindians-living in a single restricted geographical area of Ecuador, appear to have different risk factors for acquisition and clinical expression of onchocerciasis, a disease caused by the filarial parasite Onchocerca volvulus. In this study, GM and KM allotypes were determined in 25 Afro-Ecuadorians and 24 Amerindians infected with Onchocerca volvulus (INF) and in putative immune individuals (PI). In Afro-Ecuadorians, the frequency of the homozygous KM 3 phenotype was significantly decreased in INF as compared with the PI group (20 vs. 68%; P = 0.0012), while the frequency of the heterozygous KM 1,3 phenotype was increased in INF as compared with the PI subjects (48 vs 9%; P = 0.0044). These results suggest that in Afro- Ecuadorians KM 3 is associated with a lower relative risk (resistance), whereas KM 1,3 is associated with an increased risk (susceptibility) of onchocerciasis

Neurocognitive and mental health outcomes in children with tungiasis: a cross-sectional study in rural Kenya and Uganda

Background: Tungiasis, a neglected tropical parasitosis, disproportionately affects children. Few empirical studies have reported neurocognitive and mental health outcomes of children with ectoparasitic skin diseases like tungiasis. Pathophysiology of tungiasis suggests it could detrimentally affect cognition and behaviour. This study pioneered the investigation of neurocognitive and mental health outcomes in children with tungiasis. Methods: This was a multi-site cross-sectional study including 454 quasi-randomly sampled school-children aged 8–14 from 48 randomly selected schools in two counties in Kenya and a district in Uganda. The participants were stratified into infected and uninfected based on the presence of tungiasis. The infected were further classified into mild and severe infection groups based on the intensity of the infection. Adapted, validated, and standardized measures of cognition and mental health such as Raven Matrices and Child Behaviour Checklist were used to collect data. Statistical tests including a multilevel, generalized mixed-effects linear models with family link set to identity were used to compare the scores of uninfected and infected children and to identify other potential risk factors for neurocognitive and behavioural outcomes. Results: When adjusted for covariates, mild infection was associated with lower scores in literacy [adjusted β(aβ) = − 8.9; 95% confidence interval (CI) − 17.2, − 0.6], language (aβ = − 1.7; 95% CI − 3.2, − 0.3), cognitive flexibility (aβ = − 6.1; 95% CI − 10.4, − 1.7) and working memory (aβ = − 0.3; 95% CI − 0.6, − 0.1). Severe infection was associated with lower scores in literacy (aβ = − 11.0; 95% CI − 19.3, − 2.8), response inhibition, (aβ = − 2.2; 95% CI − 4.2, − 0.2), fine motor control (aβ = − 0.7; 95% CI − 1.1, − 0.4) and numeracy (aβ = − 3; 95% CI − 5.5, − 0.4). Conclusions:This study provides first evidence that tungiasis is associated with poor neurocognitive functioning in children. Since tungiasis is a chronic disease with frequent reinfections, such negative effects may potentially impair their development and life achievements

Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

Background Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. Methods We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation. Findings Between Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16–36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10−7). Interpretation These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data. Funding The National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources)

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57

Control of Tungiasis in Absence of a Roadmap: Grassroots and Global Approaches

Tungiasis is a tropical skin disease caused by the sand flea Tunga penetrans. It inflicts misery upon tens of millions of people, mostly children, across Central and South America and sub-Saharan Africa, and yet there is no globally accepted roadmap for its control. Here we review how research in the last 15 years has developed control methods and report on new grassroots and digital mapping approaches. Treatment is now possible with a two-component dimethicone, used for the treatment of headlice in Europe, Asia and Canada, but not yet available in most tungiasis-endemic areas. Prevention is possible through the daily use of repellents based on coconut oil. A Kenyan coastal community has successfully controlled tungiasis using a neem and coconut oil mix produced locally to treat cases, combined with spraying floors with neem solution and distributing closed shoes. Development of affordable hard floor technology is underway, although not yet widely available, but is a priority to control off-host stages in the floors of homes. A new web-based digital mapping application will enable researchers and health officials to collaborate, share data and map the prevalence of tungiasis. We conclude that tungiasis can be controlled through a multi-disciplinary, One Health approach