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Molecular Diagnostics for Soil-Transmitted Helminths

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      Abstract

      Historically, the diagnosis of soil-transmitted helminths (STHs) (e.g., Strongyloides stercoralis, Trichuris trichiura, Ancylostoma duodenale, Necator americanus, and Ascaris lumbricoides) has relied on often-insensitive microscopy techniques. Over the past several years, there has been an effort to use molecular diagnostics, particularly quantitative polymerase chain reaction (qPCR), to detect intestinal pathogens. While some platforms have been approved by regulatory bodies (e.g., Food and Drug Administration) to detect intestinal bacteria, viruses, and protozoa, there are no approved tests currently available for STH. Although studies comparing qPCR to microscopy methods for STH are imperfect, due in large part to a lack of a sufficient gold standard, they do show a significant increase in sensitivity and specificity of qPCR compared with microscopic techniques. These studies, as well as the advantages and disadvantages of using qPCR for STH diagnosis, are discussed. Guidelines for those designing future studies utilizing qPCR are proposed for optimizing results, as is the proposition for using standardized molecular diagnostics routinely for STH in clinical laboratories and for field-based studies when possible.

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      Basic local alignment search tool.

      A new approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair (MSP) score. Recent mathematical results on the stochastic properties of MSP scores allow an analysis of the performance of this method as well as the statistical significance of alignments it generates. The basic algorithm is simple and robust; it can be implemented in a number of ways and applied in a variety of contexts including straightforward DNA and protein sequence database searches, motif searches, gene identification searches, and in the analysis of multiple regions of similarity in long DNA sequences. In addition to its flexibility and tractability to mathematical analysis, BLAST is an order of magnitude faster than existing sequence comparison tools of comparable sensitivity.
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        Global numbers of infection and disease burden of soil transmitted helminth infections in 2010

        Background Quantifying the burden of parasitic diseases in relation to other diseases and injuries requires reliable estimates of prevalence for each disease and an analytic framework within which to estimate attributable morbidity and mortality. Here we use data included in the Global Atlas of Helminth Infection to derive new global estimates of numbers infected with intestinal nematodes (soil-transmitted helminths, STH: Ascaris lumbricoides, Trichuris trichiura and the hookworms) and use disability-adjusted life years (DALYs) to estimate disease burden. Methods Prevalence data for 6,091 locations in 118 countries were sourced and used to estimate age-stratified mean prevalence for sub-national administrative units via a combination of model-based geostatistics (for sub-Saharan Africa) and empirical approaches (for all other regions). Geographical variation in infection prevalence within these units was approximated using modelled logit-normal distributions, and numbers of individuals with infection intensities above given thresholds estimated for each species using negative binomial distributions and age-specific worm/egg burden thresholds. Finally, age-stratified prevalence estimates for each level of infection intensity were incorporated into the Global Burden of Disease Study 2010 analytic framework to estimate the global burden of morbidity and mortality associated with each STH infection. Results Globally, an estimated 438.9 million people (95% Credible Interval (CI), 406.3 - 480.2 million) were infected with hookworm in 2010, 819.0 million (95% CI, 771.7 – 891.6 million) with A. lumbricoides and 464.6 million (95% CI, 429.6 – 508.0 million) with T. trichiura. Of the 4.98 million years lived with disability (YLDs) attributable to STH, 65% were attributable to hookworm, 22% to A. lumbricoides and the remaining 13% to T. trichiura. The vast majority of STH infections (67%) and YLDs (68%) occurred in Asia. When considering YLDs relative to total populations at risk however, the burden distribution varied more considerably within major global regions than between them. Conclusion Improvements in the cartography of helminth infection, combined with mathematical modelling approaches, have resulted in the most comprehensive contemporary estimates for the public health burden of STH. These numbers form an important benchmark upon which to evaluate future scale-up of major control efforts.
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          Strongyloides stercoralis in the Immunocompromised Population.

          Strongyloides stercoralis is an intestinal nematode of humans that infects tens of millions of people worldwide. S. stercoralis is unique among intestinal nematodes in its ability to complete its life cycle within the host through an asexual autoinfective cycle, allowing the infection to persist in the host indefinitely. Under some conditions associated with immunocompromise, this autoinfective cycle can become amplified into a potentially fatal hyperinfection syndrome, characterized by increased numbers of infective filariform larvae in stool and sputum and clinical manifestations of the increased parasite burden and migration, such as gastrointestinal bleeding and respiratory distress. S. stercoralis hyperinfection is often accompanied by sepsis or meningitis with enteric organisms. Glucocorticoid treatment and human T-lymphotropic virus type 1 infection are the two conditions most specifically associated with triggering hyperinfection, but cases have been reported in association with hematologic malignancy, malnutrition, and AIDS. Anthelmintic agents such as ivermectin have been used successfully in treating the hyperinfection syndrome as well as for primary and secondary prevention of hyperinfection in patients whose exposure history and underlying condition put them at increased risk.
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            Author and article information

            Affiliations
            [ 1 ]Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
            Author notes
            *Address correspondence to Elise M. O'Connell, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4/Room B1-05, 4 Center Drive, Bethesda, MD 20892. E-mail: oconnellem@ 123456niaid.nih.gov
            Journal
            Am J Trop Med Hyg
            Am. J. Trop. Med. Hyg
            tpmd
            The American Journal of Tropical Medicine and Hygiene
            The American Society of Tropical Medicine and Hygiene
            0002-9637
            1476-1645
            07 September 2016
            07 September 2016
            : 95
            : 3
            : 508-513
            27481053 5014250 10.4269/ajtmh.16-0266
            ©The American Society of Tropical Medicine and Hygiene

            This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

            Categories
            Review Article

            Infectious disease & Microbiology

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