A Critique on Sustainable Cities Waste Management Predicaments; Case of Nairobi City, Kenya

Waste management predicaments in attaining sustainable city status globally is challenged by increased solid waste generation as a result of rapid urban population and migration. Through a critique lens, solid waste management predicaments in developing countries characterized by inefficiencies; weak institutional capacities and lack of financial prudence. Nairobi City illustrates vividly predicaments through sporadic growth of open dumpsites, blocked drainers and sewers, indiscriminate behavior of littering. This is aided by weak enforcement of solid waste policies and regulations, duplicity of mandates by institutions and limited human resources. This paper undertakes to explicate predicaments in Nairobi City County and is supported by institutional, capacity and planned behavior theories. The study adopted mixed research design with data collection from a sample size of 385 household. Primary and secondary data was collected using questionnaires, key informant interview and focus group discussion; transect walk and desk top analysis. The results support the critique as documented by this paper. The study recommends institutional empowerment to reverse negative predicaments for sustainable global cities

Juxtamembrane Shedding of Plasmodium falciparum AMA1 Is Sequence Independent and Essential, and Helps Evade Invasion-Inhibitory Antibodies

The malarial life cycle involves repeated rounds of intraerythrocytic replication interspersed by host cell rupture which releases merozoites that rapidly invade fresh erythrocytes. Apical membrane antigen-1 (AMA1) is a merozoite protein that plays a critical role in invasion. Antibodies against AMA1 prevent invasion and can protect against malaria in vivo, so AMA1 is of interest as a malaria vaccine candidate. AMA1 is efficiently shed from the invading parasite surface, predominantly through juxtamembrane cleavage by a membrane-bound protease called SUB2, but also by limited intramembrane cleavage. We have investigated the structural requirements for shedding of Plasmodium falciparum AMA1 (PfAMA1), and the consequences of its inhibition. Mutagenesis of the intramembrane cleavage site by targeted homologous recombination abolished intramembrane cleavage with no effect on parasite viability in vitro. Examination of PfSUB2-mediated shedding of episomally-expressed PfAMA1 revealed that the position of cleavage is determined primarily by its distance from the parasite membrane. Certain mutations at the PfSUB2 cleavage site block shedding, and parasites expressing these non-cleavable forms of PfAMA1 on a background of expression of the wild type gene invade and replicate normally in vitro. The non-cleavable PfAMA1 is also functional in invasion. However – in contrast to the intramembrane cleavage site - mutations that block PfSUB2-mediated shedding could not be stably introduced into the genomic pfama1 locus, indicating that some shedding of PfAMA1 by PfSUB2 is essential. Remarkably, parasites expressing shedding-resistant forms of PfAMA1 exhibit enhanced sensitivity to antibody-mediated inhibition of invasion. Drugs that inhibit PfSUB2 activity should block parasite replication and may also enhance the efficacy of vaccines based on AMA1 and other merozoite surface proteins

Cost analysis of school-based intermittent screening and treatment of malaria in Kenya

<p>Abstract</p> <p>Background</p> <p>The control of malaria in schools is receiving increasing attention, but there remains currently no consensus as to the optimal intervention strategy. This paper analyses the costs of intermittent screening and treatment (IST) of malaria in schools, implemented as part of a cluster-randomized controlled trial on the Kenyan coast.</p> <p>Methods</p> <p>Financial and economic costs were estimated using an ingredients approach whereby all resources required in the delivery of IST are quantified and valued. Sensitivity analysis was conducted to investigate how programme variation affects costs and to identify potential cost savings in the future implementation of IST.</p> <p>Results</p> <p>The estimated financial cost of IST per child screened is US$6.61 (economic cost US$ 6.24). Key contributors to cost were salary costs (36%) and malaria rapid diagnostic tests (RDT) (22%). Almost half (47%) of the intervention cost comprises redeployment of existing resources including health worker time and use of hospital vehicles. Sensitivity analysis identified changes to intervention delivery that can reduce programme costs by 40%, including use of alternative RDTs and removal of supervised treatment. Cost-effectiveness is also likely to be highly sensitive to the proportion of children found to be RDT-positive.</p> <p>Conclusion</p> <p>In the current context, school-based IST is a relatively expensive malaria intervention, but reducing the complexity of delivery can result in considerable savings in the cost of intervention.</p> <p>(Costs are reported in US$ 2010).</p

Why Functional Pre-Erythrocytic and Bloodstage Malaria Vaccines Fail: A Meta-Analysis of Fully Protective Immunizations and Novel Immunological Model

Background: Clinically protective malaria vaccines consistently fail to protect adults and children in endemic settings, and at best only partially protect infants. Methodology/Principal Findings: We identify and evaluate 1916 immunization studies between 1965-February 2010, and exclude partially or nonprotective results to find 177 completely protective immunization experiments. Detailed reexamination reveals an unexpectedly mundane basis for selective vaccine failure: live malaria parasites in the skin inhibit vaccine function. We next show published molecular and cellular data support a testable, novel model where parasite-host interactions in the skin induce malaria-specific regulatory T cells, and subvert early antigen-specific immunity to parasite-specific immunotolerance. This ensures infection and tolerance to reinfection. Exposure to Plasmodium-infected mosquito bites therefore systematically triggers immunosuppression of endemic vaccine-elicited responses. The extensive vaccine trial data solidly substantiate this model experimentally. Conclusions/Significance: We conclude skinstage-initiated immunosuppression, unassociated with bloodstage parasites, systematically blocks vaccine function in the field. Our model exposes novel molecular and procedural strategies to significantly and quickly increase protective efficacy in both pipeline and currently ineffective malaria vaccines, and forces fundamental reassessment of central precepts determining vaccine development. This has major implications fo

Gender differentiated preferences for a community-based conservation initiative

Community-based conservation (CBC) aims to benefit local people as well as to achieve conservation goals, but has been criticised for taking a simplistic view of "community" and failing to recognise differences in the preferences and motivations of community members. We explore this heterogeneity in the context of Kenya's conservancies, focussing on the livelihood preferences of men and women living adjacent to the Maasai Mara National Reserve. Using a discrete choice experiment we quantify the preferences of local community members for key components of their livelihoods and conservancy design, differentiating between men and women and existing conservancy members and non-members. While Maasai preference for pastoralism remains strong, non-livestock-based livelihood activities are also highly valued and there was substantial differentiation in preferences between individuals. Involvement with conservancies was generally perceived to be positive, but only if households were able to retain some land for other purposes. Women placed greater value on conservancy membership, but substantially less value on wage income, while existing conservancy members valued both conservancy membership and livestock more highly than did non-members. Our findings suggest that conservancies can make a positive contribution to livelihoods, but care must be taken to ensure that they do not unintentionally disadvantage any groups. We argue that conservation should pay greater attention to individuallevel differences in preferences when designing interventions in order to achieve fairer and more sustainable outcomes for members of local communities

Large-scale climatic phenomena drive fluctuations in macroinvertebrate assemblages in lowland tropical streams, Costa Rica: The importance of ENSO events in determining long-term (15y) patterns

Understanding how environmental variables influence the distribution and density of organisms over relatively long temporal scales is a central question in ecology given increased climatic variability (e.g., precipitation, ENSO events). The primary goal of our study was to evaluate long-term (15y time span) patterns of climate, as well as environmental parameters in two Neotropical streams in lowland Costa Rica, to assess potential effects on aquatic macroinvertebrates. We also examined the relative effects of an 8y whole-stream P-enrichment experiment on macroinvertebrate assemblages against the backdrop of this long-term study. Climate, environmental variables and macroinvertebrate samples were measured monthly for 7y and then quarterly for an additional 8y in each stream. Temporal patterns in climatic and environmental variables showed high variability over time, without clear inter-annual or intra-annual patterns. Macroinvertebrate richness and abundance decreased with increasing discharge and was positively related to the number of days since the last high discharge event. Findings show that fluctuations in stream physicochemistry and macroinvertebrate assemblage structure are ultimately the result of large-scale climatic phenomena, such as ENSO events, while the 8y P-enrichment did not appear to affect macroinvertebrates. Our study demonstrates that Neotropical lowland streams are highly dynamic and not as stable as is commonly presumed, with high intra- and inter-annual variability in environmental parameters that change the structure and composition of freshwater macroinvertebrate assemblages.This study was financed by National Science Foundation (DEB 1122389) to Catherine M. Pringle. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Ciencias del Mar y Limnología (CIMAR

Cardiovascular concentration-effect relationships of amodiaquine and its metabolite desethylamodiaquine: clinical and pre-clinical studies

Background Amodiaquine is a 4-aminoquinoline used extensively for the treatment and prevention of malaria. Orally administered amodiaquine is largely converted to the active metabolite desethylamodiaquine. Amodiaquine can cause bradycardia, hypotension, and electrocardiograph (ECG) QT interval prolongation but the relationship of these changes to drug concentrations is not well-characterised. Methods We conducted a secondary analysis of a pharmacokinetic study of the cardiac safety of amodiaquine (10mg base/kg/day over 3 days) in 54 Kenyan adults (≥18 years) with uncomplicated malaria. Non-linear mixed effects modelling was used to assess amodiaquine and desethylamodiaquine concentration-effect relationships for vital sign (pulse rate, blood pressure) and ECG interval (QT, QRS, PR) outcomes. We also measured the spontaneous beating heart rate after cumulative dosing of amodiaquine and desethylamodiaquine in isolated mouse atrial preparations. Results Amodiaquine and desethylamodiaquine caused concentration-dependent mean decreases in pulse rate (1.9beats/minute per 100nmol/L; 95% CI: 1.5-2.4), supine systolic blood pressure (1.7mmHg per 100nmol/L; 1.2-2.1), erect systolic blood pressure (1.5mmHg per 100nmol/L; 1.0-2.0), and erect diastolic blood pressure (1.4mmHg per 100nmol/L; 1.0-1.7). The mean QT interval prolongation was 1.4milliseconds per 100nmol/L irrespective of correction factor after adjustment for residual heart rate dependency. There was no significant effect of drug concentration on postural change in blood pressure or PR and QRS intervals. In mouse atria, the spontaneous beating rate was significantly reduced by amodiaquine (n=6) and desethylamodiaquine (n=8) at 3μmol/litre (amodiaquine:10±2%; desethylamodiaquine:12±3%) and 10μmol/litre (amodiaquine:50±7%; desethylamodiaquine:46±6%) concentrations with no significant difference in potency between the two compounds. Conclusion Amodiaquine and desethylamodiaquine have concentration-dependent effects on heart rate, blood pressure, and ventricular repolarisation