The technical genesis and practice of 8-aminoquinoline therapy of latent malaria offer singular scientific, clinical, and public health insights. The 8-aminoquinolines brought revolutionary ...scientific discoveries, dogmatic practices, benign neglect, and, finally, enduring promise against endemic malaria. The clinical use of plasmochin-the first rationally synthesized blood schizontocide and the first gametocytocide, tissue schizontocide, and hypnozoitocide of any kind-commenced in 1926. Plasmochin became known to sometimes provoke fatal hemolytic crises. World War II delivered a newer 8-aminoquinoline, primaquine, and the discovery of glucose-6-phosphate dehydrogenase (G6PD) deficiency as the basis of its hemolytic toxicity came in 1956. Primaquine nonetheless became the sole therapeutic option against latent malaria. After 40 years of fitful development, in 2018 the U.S. Food and Drug Administration registered the 8-aminoquinoline called tafenoquine for the prevention of all malarias and the treatment of those that relapse. Tafenoquine also cannot be used in G6PD-unknown or -deficient patients. The hemolytic toxicity of the 8-aminoquinolines impedes their great potential, but this problem has not been a research priority. This review explores the complex technical dimensions of the history of 8-aminoquinolines. The therapeutic principles thus examined may be leveraged in improved practice and in understanding the bright prospect of discovery of newer drugs that cannot harm G6PD-deficient patients.
J. Kevin Baird and colleagues, examine and discuss the estimated global burden of vivax malaria and it's biological, clinical, and public health complexity.
The overwhelming dominance of Duffy blood group negativity among most people living in sub-Saharan Africa has been considered the basis of their protection from endemic Plasmodium vivax malaria. New ...evidence demonstrates widespread transmission of P. vivax in Duffy-negative Africa, though currently of unknown distribution, magnitude, or consequences. Other new evidence from outside of Africa demonstrates marked tropisms of P. vivax for extravascular tissues of bone marrow and spleen. Those establish states of proliferative infection with low-grade or undetectable parasitemia of peripheral blood causing acute and chronic disease. This review examines the plausibility of those infectious processes also operating in Duffy-negative Africans and causing harm of unrecognized origin.
Plasmodium vivax transmission occurs in Duffy-negative sub-Saharan Africa at low prevalence and density of parasitemia, but conventional inference to that epidemiology and pathophysiology may underestimate its presence and harm.The strict requirement for CD71+ erythroid cells by P. vivax drives marked tropism for extravascular tissue invasion and infiltration.Infection of erythropoietic tissues of the bone marrow, spleen, and liver by P. vivax may cause severe anemia, thrombocytopenia, and hepatosplenomegaly without patent parasitemia.Parasitemia as a marker of P. vivax biomass and prevalence should be acknowledged as inadequate and dangerously misleading; optimized and validated alternative diagnostics for P. vivax are needed for the vitally important and incomplete work of estimating its burdens of infection, illness, and death.
Biological monitoring has failed to develop from simple binary assessment outcomes of the impacted/unimpacted type, towards more diagnostic frameworks, despite significant scientific effort over the ...past fifty years. It is our assertion that this is largely because of the limited information content of biological samples processed by traditional morphology‐based taxonomy, which is a slow, imprecise process, focused on restricted groups of organisms. We envision a new paradigm in ecosystem assessment, which we refer to as ‘Biomonitoring 2.0’. This new schema employs DNA‐based identification of taxa, coupled with high‐throughput DNA sequencing on next‐generation sequencing platforms. We discuss the transformational nature of DNA‐based approaches in biodiversity discovery and ecosystem assessment and outline a path forward for their future widespread application.
Current understanding of the spatial epidemiology and geographical distribution of Plasmodium vivax is far less developed than that for P. falciparum, representing a barrier to rational strategies ...for control and elimination. Here we present the first systematic effort to map the global endemicity of this hitherto neglected parasite.
We first updated to the year 2010 our earlier estimate of the geographical limits of P. vivax transmission. Within areas of stable transmission, an assembly of 9,970 geopositioned P. vivax parasite rate (PvPR) surveys collected from 1985 to 2010 were used with a spatiotemporal Bayesian model-based geostatistical approach to estimate endemicity age-standardised to the 1-99 year age range (PvPR(1-99)) within every 5×5 km resolution grid square. The model incorporated data on Duffy negative phenotype frequency to suppress endemicity predictions, particularly in Africa. Endemicity was predicted within a relatively narrow range throughout the endemic world, with the point estimate rarely exceeding 7% PvPR(1-99). The Americas contributed 22% of the global area at risk of P. vivax transmission, but high endemic areas were generally sparsely populated and the region contributed only 6% of the 2.5 billion people at risk (PAR) globally. In Africa, Duffy negativity meant stable transmission was constrained to Madagascar and parts of the Horn, contributing 3.5% of global PAR. Central Asia was home to 82% of global PAR with important high endemic areas coinciding with dense populations particularly in India and Myanmar. South East Asia contained areas of the highest endemicity in Indonesia and Papua New Guinea and contributed 9% of global PAR.
This detailed depiction of spatially varying endemicity is intended to contribute to a much-needed paradigm shift towards geographically stratified and evidence-based planning for P. vivax control and elimination.
In a rapidly changing world we need methods to efficiently assess biodiversity in order to monitor ecosystem trends. Ecological monitoring often uses plant community composition to infer quality of ...sites but conventional aboveground surveys only capture a snapshot of the actively growing plant diversity. Environmental DNA (eDNA) extracted from soil samples, however, can include taxa represented by both active and dormant tissues, seeds, pollen, and detritus. Analysis of this eDNA through DNA metabarcoding provides a more comprehensive view of plant diversity at a site from a single assessment but it is not clear which DNA markers are best used to capture this diversity. Sequence recovery, annotation, and sequence resolution among taxa were evaluated for four established DNA markers (matK, rbcL, ITS2, and the trnL P6 loop) in silico using database sequences and in situ using high throughput sequencing of 35 soil samples from a remote boreal wetland. Overall, ITS2 and rbcL are recommended for DNA metabarcoding of vascular plants from eDNA when not using customized or geographically restricted reference databases. We describe a new framework for evaluating DNA metabarcodes and, contrary to existing assumptions, we found that full length DNA barcode regions could outperform shorter markers for surveying plant diversity from soil samples. By using current DNA barcoding markers rbcL and ITS2 for plant metabarcoding, we can take advantage of existing resources such as the growing DNA barcode database. Our work establishes the value of standard DNA barcodes for soil plant eDNA analysis in ecological investigations and biomonitoring programs and supports the collaborative development of DNA barcoding and metabarcoding.
Economic growth has a potential impact on waste generation worldwide. Growing recognition for resources recovery from waste including production of a clean energy has led to the development of ...standards for, and the generation of, Solid Recovered Fuel (SRF). SRF, according to BS EN ISO 21640 is a fuel prepared from nonhazardous/treated waste to be utilized for energy recovery in incineration or co-incineration plants which meets the classification and specification. The amount of combustible fractions (i.e., plastic, textile and paper) that are present in Healthcare Waste (HCW) and Municipal Solid Waste (MSW) provides an opportunity for SRF production. HCW is defined as clinical waste generated from healthcare facilities. Limited efforts in utilizing treated HCW in production of SRF were noted, despite the fact that high content of combustible fractions, hence the novelty of this research. This research addresses the opportunities of utilizing autoclaved HCW as an alternate fuel; through a detailed chemical and physical analysis of autoclaved HCW collected from the Sultanate of Oman hospital and healthcare facilities. Furthermore, this study examines the possible uses of such materials instead of landfilling. The utilization of treated HCW as an alternative fuel is not only saving the land space, but also reduces the carbon emissions originating from landfilling. This in fact would also support the government in achieving its aspiring goal of the net zero carbon emissions by 2050 through better utilization of these materials in production of SRF as an alternative to fossil fuel combustion. The study revealed that autoclaved HCW appears to have a high quality SRF and is classified as (NCV 4, Cl 3); which complies with the potential end users' specifications. It is estimated that the combined energy output from MSW and HCW combustible fractions could cover about 12.75% of the energy requirements for Oman cement factories.
Implications: The results confirm the viability of using autoclave (HCW) as an alternative fuel due to its high thermal energy content. Based on mean Net Calorific Value (NCV) of analyzed HCW that is found around 14 (MJ/Kg
(ar)
), and the mean Cl level (i.e., 0.814 ± 0.213%
(d)
); the SRF is classified as (NCV4, Cl 3). This grade is found to be well within the end users accepted range. This opens up the opportunity for creating a market demand for HCW that not only it could boost its recovery, but it could also unlock the value that can generates.
Timely and accurate biodiversity analysis poses an ongoing challenge for the success of biomonitoring programs. Morphology-based identification of bioindicator taxa is time consuming, and rarely ...supports species-level resolution especially for immature life stages. Much work has been done in the past decade to develop alternative approaches for biodiversity analysis using DNA sequence-based approaches such as molecular phylogenetics and DNA barcoding. On-going assembly of DNA barcode reference libraries will provide the basis for a DNA-based identification system. The use of recently introduced next-generation sequencing (NGS) approaches in biodiversity science has the potential to further extend the application of DNA information for routine biomonitoring applications to an unprecedented scale. Here we demonstrate the feasibility of using 454 massively parallel pyrosequencing for species-level analysis of freshwater benthic macroinvertebrate taxa commonly used for biomonitoring. We designed our experiments in order to directly compare morphology-based, Sanger sequencing DNA barcoding, and next-generation environmental barcoding approaches. Our results show the ability of 454 pyrosequencing of mini-barcodes to accurately identify all species with more than 1% abundance in the pooled mixture. Although the approach failed to identify 6 rare species in the mixture, the presence of sequences from 9 species that were not represented by individuals in the mixture provides evidence that DNA based analysis may yet provide a valuable approach in finding rare species in bulk environmental samples. We further demonstrate the application of the environmental barcoding approach by comparing benthic macroinvertebrates from an urban region to those obtained from a conservation area. Although considerable effort will be required to robustly optimize NGS tools to identify species from bulk environmental samples, our results indicate the potential of an environmental barcoding approach for biomonitoring programs.
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