217 research outputs found

    Limitations of microscopy to differentiate Plasmodium species in a region co-endemic for Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi

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    BackgroundIn areas co-endemic for multiple Plasmodium species, correct diagnosis is crucial for appropriate treatment and surveillance. Species misidentification by microscopy has been reported in areas co-endemic for vivax and falciparum malaria, and may be more frequent in regions where Plasmodium knowlesi also commonly occurs. MethodsThis prospective study in Sabah, Malaysia, evaluated the accuracy of routine district and referral hospital-based microscopy, and microscopy performed by an experienced research microscopist, for the diagnosis of PCR-confirmed Plasmodium falciparum, P. knowlesi, and Plasmodium vivax malaria. ResultsA total of 304 patients with PCR-confirmed Plasmodium infection were enrolled, including 130 with P. knowlesi, 122 with P. falciparum, 43 with P. vivax, one with Plasmodium malariae and eight with mixed species infections. Among patients with P. knowlesi mono-infection, routine and cross-check microscopy both identified 94 (72%) patients as “P. malariae/P. knowlesi”; 17 (13%) and 28 (22%) respectively were identified as P. falciparum, and 13 (10%) and two (1.5%) as P. vivax. Among patients with PCR-confirmed P. falciparum, routine and cross-check microscopy identified 110/122 (90%) and 112/118 (95%) patients respectively as P. falciparum, and 8/122 (6.6%) and 5/118 (4.2%) as “P. malariae/P. knowlesi”. Among those with P. vivax, 23/43 (53%) and 34/40 (85%) were correctly diagnosed by routine and cross-check microscopy respectively, while 13/43 (30%) and 3/40 (7.5%) patients were diagnosed as “P. malariae/P. knowlesi”. Four of 13 patients with PCR-confirmed P. vivax and misdiagnosed by routine microscopy as “P. malariae/P. knowlesi” were subsequently re-admitted with P. vivax malaria. ConclusionsMicroscopy does not reliably distinguish between P. falciparum, P. vivax and P. knowlesi in a region where all three species frequently occur. Misdiagnosis of P. knowlesi as both P. vivax and P. falciparum, and vice versa, is common, potentially leading to inappropriate treatment, including chloroquine therapy for P. falciparum and a lack of anti-relapse therapy for P. vivax. The limitations of microscopy in P. knowlesi-endemic areas supports the use of unified blood-stage treatment strategies for all Plasmodium species, the development of accurate rapid diagnostic tests suitable for all species, and the use of PCR-confirmation for accurate surveillance

    Advanced acoustic emission source location in aircraft structural testing

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    Acoustic emission (AE) is an in situ Structural Health Monitoring (SHM) technique, where a structure is monitored for the ultrasonic waves produced due to crack growth. A major challenge with AE when applied to aircraft, and other complex structures, is that wave propagation is significantly affected by stiffeners, holes, thickness changes and other complexity. This reduces the accuracy of traditional source location techniques, that are based on a singular propagating wave speed. The Delta-T method enables higher levels of accuracy by mapping the structure and accounting for these changes. In this work AE monitoring equipment was installed on a section of an aluminium Airbus A320 wing. Location trials showed the Delta-T technique improved the average error from 85mm to 23mm, for artificial Hsu-Nielson sources, compared to the commercial standard technique. Testing under fatigue however demonstrated the challenges encountered when inspecting 3D structures (due to multiple signal paths) with significant levels of background noise. Of two cracks identified in the structure, the first of these was successfully detected and located, whilst the other was missed due to high machine noise and unrepresentative loading

    Gene expression in Leishmania is regulated predominantly by gene dosage

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    ABSTRACT Leishmania tropica, a unicellular eukaryotic parasite present in North and East Africa, the Middle East, and the Indian subcontinent, has been linked to large outbreaks of cutaneous leishmaniasis in displaced populations in Iraq, Jordan, and Syria. Here, we report the genome sequence of this pathogen and 7,863 identified protein-coding genes, and we show that the majority of clinical isolates possess high levels of allelic diversity, genetic admixture, heterozygosity, and extensive aneuploidy. By utilizing paired genome-wide high-throughput DNA sequencing (DNA-seq) with RNA-seq, we found that gene dosage, at the level of individual genes or chromosomal “somy” (a general term covering disomy, trisomy, tetrasomy, etc.), accounted for greater than 85% of total gene expression variation in genes with a 2-fold or greater change in expression. High gene copy number variation (CNV) among membrane-bound transporters, a class of proteins previously implicated in drug resistance, was found for the most highly differentially expressed genes. Our results suggest that gene dosage is an adaptive trait that confers phenotypic plasticity among natural Leishmania populations by rapid down- or upregulation of transporter proteins to limit the effects of environmental stresses, such as drug selection. IMPORTANCE Leishmania is a genus of unicellular eukaryotic parasites that is responsible for a spectrum of human diseases that range from cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL) to life-threatening visceral leishmaniasis (VL). Developmental and strain-specific gene expression is largely thought to be due to mRNA message stability or posttranscriptional regulatory networks for this species, whose genome is organized into polycistronic gene clusters in the absence of promoter-mediated regulation of transcription initiation of nuclear genes. Genetic hybridization has been demonstrated to yield dramatic structural genomic variation, but whether such changes in gene dosage impact gene expression has not been formally investigated. Here we show that the predominant mechanism determining transcript abundance differences (>85%) in Leishmania tropica is that of gene dosage at the level of individual genes or chromosomal somy

    The water-food-energy nexus in Pakistan: A biophysical and socio-economic challenge

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    We draw on previous work examining historical trends, likely future water use and food availability in Pakistan and extend the analysis to consider interactions with hydropower generation and the energy demand in food production due to pumping of groundwater for irrigation. Business-as-usual scenarios suggest growing demands for groundwater and energy use for food production as population grows rapidly. However, groundwater use is already unsustainable in many areas, and energy supply is failing to keep up with demand. Quantifying material linkages between water, food and energy provides a means to explore biophysical constraints. Characterising institutional constraints is equally important, as they can be significant barriers to effective stewardship of water, energy and food resources. The experience in Pakistan reinforces this finding, and we discuss the implications for hydrologists

    Zoonotic malaria transmission and land use change in Southeast Asia: what is known about the vectors

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    Zoonotic Plasmodium infections in humans in many Southeast Asian countries have been increasing, including in countries approaching elimination of human-only malaria transmission. Most simian malarias in humans are caused by Plasmodium knowlesi, but recent research shows that humans are at risk of many different simian Plasmodium species. In Southeast Asia, simian Plasmodium species are mainly transmitted by mosquitoes in the Anopheles leucosphyrus and Anopheles dirus complexes. Although there is some evidence of species outside the Leucosphyrus Group transmitting simian Plasmodium species, these await confirmation of transmission to humans. The vectors of monkey malarias are mostly found in forests and forest fringes, where they readily bite long-tailed and pig-tailed macaques (the natural reservoir hosts) and humans. How changing land-uses influence zoonotic malaria vectors is still poorly understood. Fragmentation of forests from logging, agriculture and other human activities is associated with increased zoonotic Plasmodium vector exposure. This is thought to occur through altered macaque and mosquito distributions and behaviours, and importantly, increased proximity of humans, macaques, and mosquito vectors. Underlying the increase in vector densities is the issue that the land-use change and human activities create more oviposition sites and, in correlation, increases availably of human blood hosts. The current understanding of zoonotic malaria vector species is largely based on a small number of studies in geographically restricted areas. What is known about the vectors is limited: the data is strongest for distribution and density with only weak evidence for a limited number of species in the Leucosphyrus Group for resting habits, insecticide resistance, blood feeding habits and larval habitats. More data are needed on vector diversity and bionomics in additional geographic areas to understand both the impacts on transmission of anthropogenic land-use change and how this significant disease in humans might be controlled
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