Sensitivity and specificity of cryptococcal antigen lateral flow assay for the diagnosis of HIV-associated cryptococcal meningitis in western Kenya

Background: HIV-associated cryptococcal meningitis carries a high case-fatality-rate in sub-Saharan Africa. Diagnostic delays partly contribute to this. Rapid point-of-care tests may facilitate speedy diagnosis. This study aimed to determine the sensitivity and specificity of urine, serum and cerebrospinal fluid (CSF) cryptococcal antigen lateral flow assay for the diagnosis of HIV-associated cryptococcal meningitis compared with the gold standard CSF culture.Methods: A cross-sectional study was conducted in the medical wards of Moi Teaching and Referral Hospital, Eldoret, Kenya. Adult (≥18years) HIV-infected in-patients suspected to have meningitis had paired samples of urine, serum and CSF collected and tested real time using the cryptococcal antigen lateral flow assay (rapid point of care test). CSF cultures were also conducted. Data were analyzed using STATA ® (Statacorp Texas USA®). Descriptive statistics were used to summarize demographic, clinical and laboratory parameters. Sensitivity and specificity of the rapid test were calculated with the CSF culture as the gold standard.Results: Of the 302 participants included 172 (57%) were female, median age 37 years (IQR 30-45). The median CD4+ cell count was 183/ul (IQR 54-333). Among 288 participants with available CSF culture results, 50(17%) had culture-confirmed cryptococcal meningitis. Urine rapid test had a sensitivity and specificity of 86 %( 95% CI 73-94) and 95.7% (95% CI 92-98) respectively. Serum rapid test had a sensitivity and specificity of 92% (95%CI 81-98) and 94.9% (95%CI 91-97) respectively. CSF rapid test had a sensitivity and specificity of 92% (95%CI 81-98%) and 94.5% (95% CI 91-97) respectively. Conclusion: Serum and CSF cryptococcal antigen lateral flow assay are highly sensitive and specific for the diagnosis of HIV-associated cryptococcal meningitis. Urine is relatively sensitive and specific. Serum and CSF cryptococcal antigen lateral flow assay can be used as a less expensive alternative to cryptococcal antigen latex agglutination method. Urine cryptococcal antigen lateral flow assay could be adopted as a rapid point of care diagnostic test in primary care clinics in low income settings without experience in handling CSF or serum, to fast track diagnosis of cryptococcal meningitis

Surgical Aspects of Genitourinary Bilharzia

The blood fluke Schistosoma haematobium mainly affects the lower genitourinary tract, where the pathological effects are a result of the reaction to the schistosome ova. The chronic effects cause damage to the musculature of the urinary tract resulting in scarring and fibrosis. The ureters dilate and or stricture. Contracture of the bladder and or detrussor failure may occur. Secondary calculi in the upper tracts and bladder are common. There is strong association with bladder cancer development of the squamous cell type. Emphasis is on the prevention of the infestation

Compositional and Thickness Effects on the Optical Properties of Zinc–Doped Selenium–Antimony Thin Films

Chalcogenide system of antimony (Sb)-selenium (Se)-zinc (Zn) system is a promising semiconductor for phase change memory devices due to its thermal stability and low power consumption. The study investigated the effect of film thickness and zinc content on the optical properties of thermally evaporated Sb10Se90-xZnx (x = 0, 5, 10 & 15 at. %) thin films. It was found that transmittance (T~ 85-40%) and optical band gap energy (Eopt ~ 1.60 eV – 1.22 eV) decreased but absorption coefficient (α~0.840–2.031 104 cm–1) increased with increase in zinc content. Furthermore, as the film thickness increased from 53 ± 5 nm to 286 ± 10 nm, transmittance decreased but band gap energy increased due to zinc defects and localized states in the Sb10Se90-xZnx system.Keywords: Selenium; phase change memory; localized state

Sensitive detection of EBV microRNAs across cancer spectrum reveals association with decreased survival in adult acute myelocytic leukemia

Epstein Barr virus (EBV) is the etiologic agent involved in numerous human cancers. After infecting the host, EBV establishes a latent infection, with low levels of messenger RNA (mRNA) and protein expression, evolved to evade immune recognition. Conversely, EBV microRNAs (miRNA) are expressed ubiquitously and abundantly within infected cells. Their role in tumor biology and clinical outcomes across the spectrum of cancer is not fully explained. Here, we applied our bioinformatics pipeline for quantitative EBV miRNA detection to examine sequencing data of 8,955 individual tumor samples across 27 tumor types representing the breadth of cancer. We uncover an association of intermediate levels of viral miRNA with decreased survival in adult acute myeloid leukemia (AML) patients (P = 0.00013). Prognostic modeling of this association suggests that increased EBV miRNA levels represent an independent risk factor for poor patient outcomes. Furthermore, we explore differences in expression between elevated and absent viral miRNA loads in adult AML tumors finding that EBV positivity was associated with proinflammatory signals. Together, given no associations were found for pediatric AML, our analyses suggests EBV positivity has the potential for being a prognostic biomarker and might represent a surrogate measure related to immune impairment in adult patients

Differential Gene Expression Analysis and Clinical Correlations within Endemic Burkitt Lymphoma

Endemic Burkitt lymphoma (eBL) is the most common pediatric cancer in equatorial Africa and is associated with malaria and Epstein-Barr virus co-infections. Molecular alterations within the eBL tumor genome and transcriptome have not been adequately investigated or compared to sporadic Burkitt lymphoma (sBL). Given that eBL has distinct clinical presentations in the jaw as opposed to the abdomen which are associated with survival, we hypothesize that transcriptome sequencing (RNA-seq) and potentially underlying genetic alterations will enhance our understanding of pathogenesis. Our results compare genome-wide RNA transcript abundances between eBL tumors from children (ages 6-7 yrs) with Stage I (Jaw tumor, n=14) and Stage II (abdominal, n=24) disease from Western Kenya to previously published work analyzing sBL which present in older children residing in developed countries and that tend not to be associated with EBV. Our initial analysis confirms mutational changes with likely functional alterations in the genes ID3 and TCF3, the key regulators of oncogenic pathways implicated in BL. However, the specific mutations observed in sBL are at lower frequency within eBL cases. This work represents the first comprehensive gene expression profile analysis of different eBL tumors. Hierarchical clustering, gene ontology and pathway analysis will provide insight into pathogenesis and new targets for chemotherapy

Integrative microRNA and mRNA deep-sequencing expression profiling in endemic Burkitt lymphoma

BACKGROUND: Burkitt lymphoma (BL) is characterized by overexpression of the c-myc oncogene, which in the vast majority of cases is a consequence of an IGH/MYC translocation. While myc is the seminal event, BL is a complex amalgam of genetic and epigenetic changes causing dysregulation of both coding and non-coding transcripts. Emerging evidence suggest that abnormal modulation of mRNA transcription via miRNAs might be a significant factor in lymphomagenesis. However, the alterations in these miRNAs and their correlations to their putative mRNA targets have not been extensively studied relative to normal germinal center (GC) B cells. METHODS: Using more sensitive and specific transcriptome deep sequencing, we compared previously published small miRNA and long mRNA of a set of GC B cells and eBL tumors. MiRWalk2.0 was used to identify the validated target genes for the deregulated miRNAs, which would be important for understanding the regulatory networks associated with eBL development. RESULTS: We found 211 differentially expressed (DE) genes (79 upregulated and 132 downregulated) and 49 DE miRNAs (22 up-regulated and 27 down-regulated). Gene Set enrichment analysis identified the enrichment of a set of MYC regulated genes. Network propagation-based method and correlated miRNA-mRNA expression analysis identified dysregulated miRNAs, including miR-17~95 cluster members and their target genes, which have diverse oncogenic properties to be critical to eBL lymphomagenesis. Central to all these findings, we observed the downregulation of ATM and NLK genes, which represent important regulators in response to DNA damage in eBL tumor cells. These tumor suppressors were targeted by multiple upregulated miRNAs (miR-19b-3p, miR-26a-5p, miR-30b-5p, miR-92a-5p and miR-27b-3p) which could account for their aberrant expression in eBL. CONCLUSION: Combined loss of p53 induction and function due to miRNA-mediated regulation of ATM and NLK, together with the upregulation of TFAP4, may be a central role for human miRNAs in eBL oncogenesis. This facilitates survival of eBL tumor cells with the IGH/MYC chromosomal translocation and promotes MYC-induced cell cycle progression, initiating eBL lymphomagenesis. This characterization of miRNA-mRNA interactions in eBL relative to GC B cells provides new insights on miRNA-mediated transcript regulation in eBL, which are potentially useful for new improved therapeutic strategies

Development and utilization of a decision support tool for the optimization of fertilizer application in smallholder farms in Uganda

This paper presents the development and pilot of the Fertilizer Optimization Tool (FOT), a decision support tool for use by extension agents in  advising smallholder farmers in Uganda in applying optimum (rather than maximum) fertilizer by considering the farmers’ financial abilities. The FOT is made up of three components which includes, the optimizer tool, the nutrient substitution table, and a fertilizer calibration tool. The FOT was developed using field trial data collected on specific agro-ecological zones and mapped using global positioning systems in 13 Sub-Saharan Africa countries. The FOT provides site- and farmer-specific fertilizer recommendations, providing both economic and environmental benefits. Results are based on a survey of 241 households, 57 technical personnel and tracking of 33 FOT users over a 3-season period. Results show a progressive shift in farmers’ attitude towards the value of fertilizer. More FOT users (71%) disagreed with the statement that fertilizers destroy soils, compared with  non-FOT users (52%). Crop yields (tons/ha) were significantly higher for crops receiving fertilizers compared to those not. While it is generally accepted that using fertilizer improves crop response and achieves better yields, the value of FOT was reported in terms of rationalization of investment by farmers. The average seasonal investment was approx. $43, giving a return on investment of over 107%. Given the evidence  generated from Uganda, there is a need for considering out scaling the FOT technology to other countries in Africa, which are faced with the same challenges of low fertilizer use among smallholder farmers. Using the mobile FOT app provides a further cost-effective opportunity to out scale the approach to benefit more smallholder farmers in sub-Saharan Africa. Further development of the FOT is suggested, particularly in the wake of increased focus on multi-nutrient fertilizer blends, and the need to adjust for soil PH, moisture, and long-term impacts of nutrient substitution. Key words: decision support tool, fertilizer optimization tool, precision agriculture, site-specific fertilizer recommendation

Odera Oruka in the Twenty-first Century

The late Kenyan Prof. H. Odera Oruka (1944-1995), from his base in the Department of Philosophy and Religious Studies at the University of Nairobi, contributed significantly to the growth of contemporary African philosophy, and helped locate African philosophy within the global philosophical discourse. His work in areas such as normative and applied ethics, political philosophy, epistemology, and, most notably, philosophic sagacity, continues to play a pivotal role in the current discourse on African philosophy. Prof. Oruka was also one of the founders of Thought and Practice: A Journal of the Philosophical Association of Kenya. The chapters in this volume examine various aspects of Oruka’s prolific contribution to philosophy in general, and to African philosophy in particular. Earlier versions of the chapters were presented at the three-day Odera Oruka International Symposium held from 19th to 21st November 2013, organised by the Department of Philosophy and Religious Studies at the University of Nairobi in collaboration with the Goethe Institute

Epstein Barr virus genomes reveal population structure and type 1 association with endemic Burkitt lymphoma [preprint]

Endemic Burkitt lymphoma (eBL), the most prevalent pediatric cancer in sub-Saharan Africa, is associated with malaria and Epstein Barr virus (EBV). In order to better understand the role of EBV in eBL, we improved viral DNA enrichment methods and generated a total of 98 new EBV genomes from both eBL cases (N=58) and healthy controls (N=40) residing in the same geographic region in Kenya. Comparing cases and controls, we found that EBV type 1 was significantly associated with eBL with 74.5% of patients (41/55) versus 47.5% of healthy children (19/40) carrying type 1 (OR=3.24, 95% CI=1.36 - 7.71, P=0.007). Controlling for EBV type, we also performed a genome-wide association study identifying 6 nonsynonymous variants in the genes EBNA1, EBNA2, BcLF1, and BARF1 that were enriched in eBL patients. Additionally, we observed that viruses isolated from plasma of eBL patients were identical to their tumor counterpart consistent with circulating viral DNA originating from the tumor. We also detected three intertypic recombinants carrying type 1 EBNA2 and type 2 EBNA3 regions as well as one novel genome with a 20 kb deletion resulting in the loss of multiple lytic and virion genes. Comparing EBV types, genes show differential variation rates as type 1 appears to be more divergent. Besides, type 2 demonstrates novel substructures. Overall, our findings address the complexities of EBV population structure and provide new insight into viral variation, which has the potential to influence eBL oncogenesis