In silico characterisation of putative Plasmodium falciparum vaccine candidates in African malaria populations.

Genetic diversity of surface exposed and stage specific Plasmodium falciparum immunogenic proteins pose a major roadblock to developing an effective malaria vaccine with broad and long-lasting immunity. We conducted a prospective genetic analysis of candidate antigens (msp1, ama1, rh5, eba175, glurp, celtos, csp, lsa3, Pfsea, trap, conserved chrom3, hyp9, hyp10, phistb, surfin8.2, and surfin14.1) for malaria vaccine development on 2375 P. falciparum sequences from 16 African countries. We described signatures of balancing selection inferred from positive values of Tajima's D for all antigens across all populations except for glurp. This could be as a result of immune selection on these antigens as positive Tajima's D values mapped to regions with putative immune epitopes. A less diverse phistb antigen was characterised with a transmembrane domain, glycophosphatidyl anchors between the N and C- terminals, and surface epitopes that could be targets of immune recognition. This study demonstrates the value of population genetic and immunoinformatic analysis for identifying and characterising new putative vaccine candidates towards improving strain transcending immunity, and vaccine efficacy across all endemic populations.

Erratum: Whole genome analysis of local Kenyan and global sequences unravels the epidemiological and molecular evolutionary dynamics of RSV genotype ON1 strains.

[This corrects the article DOI: 10.1093/ve/vey027.][This corrects the article DOI: 10.1093/ve/vey027.].

Whole genome analysis of local Kenyan and global sequences unravels the epidemiological and molecular evolutionary dynamics of RSV genotype ON1 strains.

The respiratory syncytial virus (RSV) group A variant with the 72-nucleotide duplication in the G gene, genotype ON1, was first detected in Kilifi in 2012 and has almost completely replaced circulating genotype GA2 strains. This replacement suggests some fitness advantage of ON1 over the GA2 viruses in Kilifi, and might be accompanied by important genomic substitutions in ON1 viruses. Close observation of such a new virus genotype introduction over time provides an opportunity to better understand the transmission and evolutionary dynamics of the pathogen. We have generated and analysed 184 RSV-A whole-genome sequences (WGSs) from Kilifi (Kenya) collected between 2011 and 2016, the first ON1 genomes from Africa and the largest collection globally from a single location. Phylogenetic analysis indicates that RSV-A circulation in this coastal Kenya location is characterized by multiple introductions of viral lineages from diverse origins but with varied success in local transmission. We identified signature amino acid substitutions between ON1 and GA2 viruses' surface proteins (G and F), polymerase (L), and matrix M2-1 proteins, some of which were positively selected, and thereby provide an enhanced picture of RSV-A diversity. Furthermore, five of the eleven RSV open reading frames (ORFs) (G, F, L, N, and P) formed distinct phylogenetic clusters for the two genotypes. This might suggest that coding regions outside of the most frequently studied G ORF also play a role in the adaptation of RSV to host populations, with the alternative possibility that some of the substitutions are neutral and provide no selective advantage. Our analysis provides insight into the epidemiological processes that define RSV spread, highlights the genetic substitutions that characterize emerging strains, and demonstrates the utility of large-scale WGS in molecular epidemiological studies.

Moisture adsorption properties and shelf-life estimation of dried and pulverised edible house cricket Acheta domesticus (L.) and black soldier fly larvae Hermetia illucens (L.).

Edible insects are part of the diets of a significant proportion of rural populations in the tropics especially Africa and Asia, and their use as source of key nutrients for better nutrition is re-emerging. Indigenously, elemental methods are used to process the insects before they are consumed or sold in retail outlets. In recent years, better knowledge of processing, packaging and storage has become necessary because of commercialisation needs. A common processing approach involves drying after a brief heat-treatment step, and then milling into a powdered product which is sold to manufacturers or consumers as ingredient for processing final products. The hydration properties of dried powders of edible house cricket and black soldier fly larvae (BSFL) were studied with the aim of predicting shelf-life stability under typical packaging and storage temperatures experienced in the tropics. Moisture adsorption isotherms were determined gravimetrically at 25, 30 and 35 °C, over 0.11-0.97 water activity (aW) range, and the data fitted to various models. Sorption isotherms were of type II according to Brunauer classification indicating monolayer-multilayer sorption behaviour. Cricket powder exhibited higher hydration capacity, and aW of this product was less sensitive to temperature variation as compared to BSFL powder. In the two products, water exhibited transitions from bound- to free- state at ~5 g/100 g moisture content. Based on Heiss-Eichner model, a shelf-life of 7 months at 25 °C can be achieved if the cricket and BSFL powders are dried to ca. 5 g/100 g moisture content and packaged in 80 µm thick polyethylene films. At 35 °C the shelf-life of the cricket product is shortened three- to four-fold whereas the BSFL powder is unable to store.

THE DETERMINANTS OF HEALTH RELATED QUALITY OF LIFE OF PATIENTS ON MAINTENANCE HAEMODIALYSIS AT KENYATTA NATIONAL HOSPITAL, KENYA.

BACKGROUND: Health related quality of life (HRQOL) is increasingly being recognised as a primary outcome measure in the treatment of end stage renal disease. In addition to being an important surrogate marker of quality of care in patients on maintenance haemodialysis, HRQOL measures have being shown to be robust predictors of mortality and morbidity. OBJECTIVE: To determine the health related quality of life and its determinants in patients on maintenance haemodialysis at the Kenyatta National Hospital. DESIGN: A cross-sectional descriptive study. SETTING: Renal unit, Kenyatta National Hospital. SUBJECTS: Adult patients with end stage renal disease on maintenance haemodialysis. RESULTS: The mean physical composite summary and mental composite summary scores were 39.09 ± 9.49 and 41.87 ± 10.56 respectively. The burden of kidney disease sub-scale, symptom and problems sub-scale and effect of kidney disease on daily life sub-scale scores were 16.15 ± 21.83, 73.46 ± 18.06 and 67.63 ± 23.45 respectively. No significant correlations were found between the health-related quality of life scores, socio-demographic and clinical factors assessed. CONCLUSION: The health-related quality of life of patients on maintenance haemodialysis is reduced. The physical quality of life is more affected than the mental quality of life. No independent determinants of health-related quality of life were identified.

HEALTH RELATED QUALITY OF LIFE OF PATIENTS ON MAINTENANCE HAEMODIALYSIS AT KENYATTA NATIONAL HOSPITAL.

BACKGROUND: Health related quality of life is increasingly being recognised as a primary outcome measure in treatment of end-stage renal disease. The health related quality of life of patients on maintenance haemodialysis is reduced. Several interventions directed at modifiable risk factors have been shown to improve quality of life of patients on haemodialysis. OBJECTIVE: To assess the health-related quality of life of patients on maintenance haemodialysis at the Kenyatta National Hospital. DESIGN: Cross sectional descriptive study. SETTING: Kenyatta National Hospital, Renal Unit. SUBJECTS: The study was conducted on 96 patients with end-stage renal disease on maintenance haemodialysis. Socio-demographic and clinical factors were recorded for all patients. Health-related quality of life was assessed using the Kidney Disease Quality of Life-36 questionnaire. Two summary scores and three subscale scores were calculated. RESULTS: The mean physical composite summary andmental composite summary scores were 39.09 ± 9.49 and 41.87 ± 10.56 respectively. The burden of kidney disease subscale, symptom and problems subscale and effect of kidney disease on daily life subscale scores were 16.15 ± 21.83, 73.46 ± 18.061 and 67.63 ± 23.45 respectively. CONCLUSION: Health-related quality of life of patients on maintenance haemodialysis is reduced. The physical quality of life is more affected than the mental quality of life. The burden of kidney disease subscale is the most affected subscale score.

Dynamic regulation of ROCK in tumor cells controls CXCR4-driven adhesion events.

CXCR4 is a chemokine receptor often found aberrantly expressed on metastatic tumor cells. To investigate CXCR4 signaling in tumor cell adhesion, we stably overexpressed CXCR4 in MCF7 breast tumor cells. Cell attachment assays demonstrate that stimulation of the receptor with its ligand, CXCL12, promotes adhesion of MCF7-CXCR4 cells to both extracellular matrix and endothelial ligands. To more closely mimic the conditions experienced by a circulating tumor cell, we performed the attachment assays under shear stress conditions. We found that CXCL12-induced tumor cell attachment is much more pronounced under flow. ROCK is a serine/threonine kinase associated with adhesion and metastasis, which is regulated by CXCR4 signaling. Thus, we investigated the contribution of ROCK activity during CXC12-induced adhesion events. Our results demonstrate a biphasic regulation of ROCK in response to adhesion. During the initial attachment, inhibition of ROCK activity is required. Subsequently, re-activation of ROCK activity is required for maturation of adhesion complexes and enhanced tumor cell migration. Interestingly, CXCL12 partially reduces the level of ROCK activity generated by attachment, which supports a model in which stimulation with CXCL12 regulates tumor cell adhesion events by providing an optimal level of ROCK activity for effective migration.

Informed consent for clinical trials: a review.

OBJECTIVE: To identify and highlight challenges related to informed consent process for clinical trials in sub-Saharan Africa. DATA SOURCES: Published original research findings and reviews in the English literature, together with anecdotal information from our current professional experiences with clinical trials. DESIGN: Review of peer-reviewed articles. DATA EXTRACTION: Online searches were done and requests for reprints from corresponding authors and institutional subscription. DATA SYNTHESIS: Information categorised accordingly. RESULTS: Informed consent for clinical trials conducted in sub-Saharan Africa (SSA) is not always "truly informed" or "truly voluntary". Guidelines for obtaining informed consent are often difficult to implement because of low literacy levels, socio-economic and cultural factors. The local ethics committees, whose role is critical in informed consent, are weak, ill-equipped or non-existent in some countries. Many participants may have incomplete understanding of the various aspects of the clinical trials due to language barriers, the way information is disclosed or terms used for informed consent documents. In some settings, clinical trials are the only access to health care services for the local population. Further, participants may enroll with perceived notion of cure of their conditions, for monetary or material benefits. CONCLUSIONS: There is need for national guidelines on clinical research including ethics review, compensation of subjects, requirements for research investigators, facilities and ethics committees as well as budgetary allocation. These guidelines must not only address specific and unique local circumstances but also meet minimum international clinical research standards. Local bioethics and research capacity should be developed and strengthened with research sponsors contributing towards this. Local research is needed on the validity and reliability of informed consent for clinical trials and factors influencing that in different socio-cultural settings in SSA.

Malaria Diagnosis in the Community: Challenges and Potential Role of Rapid Diagnostic Tests (RDTs) in the African Region

At present; malaria rapid diagnostic tests (RDTs) are widely available and used in parts of Asia and Latin America. In Africa; their use has been limited mainly to private health facilities. With the adoption of artemisinin combination therapies (ACTs) by most African countries as first line treatment for malaria; an effective; but expensive treatment is available; and the case for an expanded role for rapid diagnostics in the fight against malaria is clear. Despite this perceived potential role for RDTs; some challenges hinder their introduction and scale-up in the public health sector. Among the requirements are significant investments in policy development; training; infrastructure; and supply chain and quality assurance systems

Roll Back Malaria and the New Partnership for Africa's Development: Is there Potential for Synergistic Collaboration in Partnerships?

This synopsis seeks to highlight and promote the enormous potential that exists between these two initiatives that seek to address closely related issues and targeting the same populations at risk within a fairly well defined geographical setting. It also attempts to argue that malaria control; just like HIV-Aids control be given high priority in the New Partnership for Africa's Development (NEPAD) health agenda; as current statistics indicate that malaria is again on the rise. While much attention and billions of dollars have rightly been given to HIV-Aids research; treatment and prevention; malaria; and not Aids; is the region's leading cause of morbidity and mortality for children under the age of five years. This is the bad news. The good news is that unlike Aids; malaria treatment and prevention are relatively cheap. In addition; there is a payback to fighting malaria; support aimed directly at improving health; rather than poverty reduction; may be a more effective way of helping Africa to thrive. Robust and sustained growth may come to Africa through a mosquito net; Artemisinin-based Combination Therapies (ACTs) or a malaria vaccine; rather that a donor's cheque for economic development initiatives

Indirect evidence from DNA sequence diversity for genetic degeneration of the Y-chromosome in dioecious species of the plant Silene: the SlY4/SlX4 and DD44-X/DD44-Y gene pairs.

The action of natural selection is expected to reduce the effective population size of a nonrecombining chromosome, and this is thought to be the chief factor leading to genetic degeneration of Y-chromosomes, which cease recombining during their evolution from ordinary chromosomes. Low effective population size of Y chromosomes can be tested by studying DNA sequence diversity of Y-linked genes. In the dioecious plant, Silene latifolia, which has sex chromosomes, one comparison (SlX1 vs. SlY1) indeed finds lower Y diversity compared with the homologous X-linked gene, and one Y-linked gene with no X-linked homologue has lower species-wide diversity than a homologous autosomal copy (SlAp3Y vs. SlAp3A). To test whether this is a general pattern for Y-linked genes, we studied two further recently described X and Y homologous gene pairs in samples from several populations of S. latifolia and S. dioica. Diversity is reduced for both Y-linked genes, compared with their X-linked homologues. Our new data are analysed to show that the low Y effective size cannot be explained by different levels of gene flow for the X vs. the Y chromosomes, either between populations or between these closely related species. Thus, all four Y-linked genes that have now been studied in these plants (the two studied here, and two previously studied genes, have low diversity). This supports other evidence for an ongoing degeneration process in these species.