17
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Age trends in asymptomatic and symptomatic Leishmania donovani infection in the Indian subcontinent: A review and analysis of data from diagnostic and epidemiological studies

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Age patterns in asymptomatic and symptomatic infection with Leishmania donovani, the causative agent of visceral leishmaniasis (VL) in the Indian subcontinent (ISC), are currently poorly understood. Age-stratified serology and infection incidence have been used to assess transmission levels of other diseases, which suggests that they may also be of use for monitoring and targeting control programmes to achieve elimination of VL and should be included in VL transmission dynamic models. We therefore analysed available age-stratified data on both disease incidence and prevalence of immune markers with the aim of collating the currently available data, estimating rates of infection, and informing modelling and future data collection.

          Methodology/Principal findings

          A systematic literature search yielded 13 infection prevalence and 7 VL incidence studies meeting the inclusion criteria. Statistical tests were performed to identify trends by age, and according to diagnostic cut-off. Simple reversible catalytic models with age-independent and age-dependent infection rates were fitted to the prevalence data to estimate infection and reversion rates, and to test different hypotheses about the origin of variation in these rates. Most of the studies showed an increase in infection prevalence with age: from 10% seroprevalence (<20% Leishmanin skin test (LST) positivity) for 0-10-year-olds to >10% seroprevalence (>20% LST-positivity) for 30-40-year-olds, but overall prevalence varied considerably between studies. VL incidence was lower amongst 0-5-year-olds than older age groups in most studies; most showing a peak in incidence between ages 5 and 20. The age-independent catalytic model provided the best overall fit to the infection prevalence data, but the estimated rates for the less parsimonious age-dependent model were much closer to estimates from longitudinal studies, suggesting that infection rates may increase with age.

          Conclusions/Significance

          Age patterns in asymptomatic infection prevalence and VL incidence in the ISC vary considerably with geographical location and time period. The increase in infection prevalence with age and peaked age-VL-incidence distribution may be due to lower exposure to infectious sandfly bites in young children, but also suggest that acquired immunity to the parasite increases with age. However, poor standardisation of serological tests makes it difficult to compare data from different studies and draw firm conclusions about drivers of variation in observed age patterns.

          Author summary

          As the elimination target for visceral leishmaniasis (VL) in the Indian subcontinent (<1 case/10,000 people/year) is approached, there is a growing need for surveillance tools with which to monitor transmission to ensure the target is sustained, especially given the large proportion of infections which are asymptomatic (~75–95%). One potential approach to estimate underlying transmission patterns may be to track age patterns in infection or cumulative exposure using diagnostic tests. However, current understanding of age patterns in asymptomatic infection and clinical VL is poor, in particular regarding possible age-dependence of infection rates. Our systematic review and pooled-analysis of age-stratified data on infection prevalence and disease incidence suggests that available diagnostics, as currently implemented, fail to meet the requirements for a reliable tool for assessing transmission, due to inconsistent standardisation and highly variable age-prevalence patterns across different settings. It also finds weak evidence for infection rates increasing with age, though further longitudinal studies are needed to test this hypothesis and to assess whether properly standardised diagnostic tests could be used to monitor ongoing transmission.

          Related collections

          Most cited references71

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Genetic diversity among Plasmodium falciparum field isolates in Pakistan measured with PCR genotyping of the merozoite surface protein 1 and 2

          Background The genetic diversity of Plasmodium falciparum has been extensively studied in various parts of the world. However, limited data are available from Pakistan. This study aimed to establish molecular characterization of P. falciparum field isolates in Pakistan measured with two highly polymorphic genetic markers, i.e. the merozoite surface protein 1 (msp-1)and 2 (msp-2). Methods Between October 2005 and October 2007, 244 blood samples from patients with symptomatic blood-slide confirmed P. falciparum mono-infections attending the Aga Khan University Hospital, Karachi, or its collection units located in Sindh and Baluchistan provinces, Pakistan were collected. The genetic diversity of P. falciparum was analysed by length polymorphism following gel electrophoresis of DNA products from nested polymerase chain reactions (PCR) targeting block 2 of msp-1 and block 3 of msp-2, including their respective allelic families KI, MAD 20, RO33, and FC27, 3D7/IC. Results A total of 238/244 (98%) patients had a positive PCR outcome in at least one genetic marker; the remaining six were excluded from analysis. A majority of patients had monoclonal infections. Only 56/231 (24%) and 51/236 (22%) carried multiple P. falciparum genotypes in msp-1 and msp-2, respectively. The estimated total number of genotypes was 25 msp-1 (12 KI; 8 MAD20; 5 RO33) and 33 msp-2 (14 FC27; 19 3D7/IC). Conclusions This is the first report on molecular characterization of P. falciparum field isolates in Pakistan with regards to multiplicity of infection. The genetic diversity and allelic distribution found in this study is similar to previous reports from India and Southeast Asian countries with low malaria endemicity.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Complexities of Assessing the Disease Burden Attributable to Leishmaniasis

            Among parasitic diseases, morbidity and mortality caused by leishmaniasis are surpassed only by malaria and lymphatic filariasis. However, estimation of the leishmaniasis disease burden is challenging, due to clinical and epidemiological diversity, marked geographic clustering, and lack of reliable data on incidence, duration, and impact of the various disease syndromes. Non-health effects such as impoverishment, disfigurement, and stigma add to the burden, and introduce further complexities. Leishmaniasis occurs globally, but has disproportionate impact in the Horn of Africa, South Asia and Brazil (for visceral leishmaniasis), and Latin America, Central Asia, and southwestern Asia (for cutaneous leishmaniasis). Disease characteristics and challenges for control are reviewed for each of these foci. We recommend review of reliable secondary data sources and collection of baseline active survey data to improve current disease burden estimates, plus the improvement or establishment of effective surveillance systems to monitor the impact of control efforts.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              The Frontiers Publishing Paradigm

              Digital technology has created the possibility of a paradigm shift in scientific publishing for the first time in four centuries. Traditional, high impact publishing largely relies on the publication of only a limited number of papers, which are highly selected by the editors and reviewers aiming at the highest “impact” on the field. As a consequence, the journal's publications may be frequently referenced by investigators in the field, much to the benefit of a journal's impact factor. In general, a high impact factor is sought after by the publishers and scientists alike as the gold standard of the excellence of the journal, promoting the widest distribution of new findings to the scientific community and essentially giving the publisher a reputation without regard to any individual articles. For a restricted-access journal, a high impact factor is of course further desirable to promote subscriptions and advertising, and eventually ensure a lucrative return. In a way, the traditional restricted-access system of scientific publishing is geared to reject submitted papers, forcing a bet between the high cost of printing what may be a “mediocre” scientific article and the assignment of a high impact factor which translates directly into revenue. Most of the highest impact journals publish only ∼10% of the papers submitted for review, and proudly tout these numbers as a sign of their exclusivity. For example, Science states that “Because of the stiff competition for space in the journal, Science now accepts less than 8% of the original research papers submitted. About 80% of submitted manuscripts are rejected during an initial screening stage by the Staff Editors and the Board of Reviewing Editors” (see Science info for authors – FAQ). In this author's opinion, this system of peer review is flawed. In order to reduce the number of manuscripts sent for review, so as to reduce the workload, editors who are not, or no longer, practicing scientists, make the editorial decision whether to send a paper for review. This decision is often driven by the familiarity of the editor with the topic or the fame of the authors of the manuscript, and not necessarily based on a thorough reading and understanding of the contents of the paper. Accordingly, many submitted papers do not make it past this first “cut.” A manuscript that does make it into the review system can easily become the victim of politics within the scientific community, as the reviewers and authors are often directly competing groups. The reviewer then wields formidable power in rejecting or delaying the acceptance of a manuscript as long as possible, making the time interval from submission to eventual publication over 1 year. The reviewers may request additional experiments and data for completely valid scientific reasons to improve the manuscript, but do not necessarily realize that at some point the authors are forced to compromise the quality of the figures or clarity of the explanations in order to still abide by journal-imposed length restrictions. This has led to supplementary online material (SOM) flourishing over the past decade, with one of my own recently submitted manuscripts weighing in at more than 85 pages. The pointless irony of all these flaws in the traditional restricted-access publishing system is that everything is based on an outdated business model of the print technology. The question we must ask ourselves is whether we can evolve from the established “restricted-access,” reader-funded publishing practice to an “open access,” author-funded publishing industry managed by scientists themselves by leveraging the internet age. In this regard, it is noteworthy that the costs of publishing with Frontiers are equivalent to the “page charges” levied by the traditional restricted-access publishers. In the Frontiers review process, authors submit their manuscripts to the Associate Editors, who assign two Review Editors for most manuscript types. These editors are charged with evaluating and certifying, in the most rigorous way, the accuracy of articles to ensure the dissemination of as much of the total amount of scientific information as possible. To facilitate this process, the Frontiers review forum has been designed to foster interaction between authors and review editors, with the overall goal of improving the manuscript – rather than finding flaws with the intention to reject. This renders the peer review process interactive and author-friendly for the first time. Review Editors are responsible for the validating the flawlessness of the experiments performed and data presented, and for the legibility and clarity of the manuscript. If the Review Editors have uncovered issues with the manuscript, the Review Editors communicate anonymously in a blog-style discussion forum with the authors to resolve the issues. If a consensus is reached with the issues resolved to the satisfaction of both of the Review Editors and the authors, the Associate Editor can accept the manuscript. One important departure from the traditional publishing system is that if the manuscript is accepted and published, the reviewers’ names are also published, thereby ensuring reviewer transparency and objectivity. This is the point where the Frontiers publishing paradigm shifts 180° from the old-fashioned traditional publishing methods. The editors are charged with using their experience and expertise to improve the manuscript to the stage where it is acceptable for publication, and not to simply reject it out of hand! However, if the issues cannot be reconciled to the satisfaction of everyone, then the manuscript is rejected and the reviewers remain anonymous to the authors. Obviously, quantity does not equal quality, and researchers entrenched in the traditional publishing paradigm are often initially suspicious that the author-pay open access model will fail to safeguard quality. Scientific reputations are, after all, derived from the quality as well as the quantity of one's publications, and therefore, the reputations of both authors and Frontiers are on the line. Accordingly, Frontiers has adopted the motto of The New York Times, “All the news fit to print,” so that Frontiers in Immunology will accept and publish “All the science deserved to be known!” Another growth of the grassroots Frontiers publishing paradigm is the tiered publishing system, a democratic meritocracy highlighting the quality of individual papers deemed important by the entire community of scientists. Article-level metrics based on actual views and downloads replace the journal-level impact factor that is calculated from the number of references to the entire journal. Authors can follow their own papers’ Impact Stats from the date of acceptance. Over the first 6 months after publication, the number of times an individual paper is accessed, and the number of times it is downloaded, is tracked electronically. The authors of the most accessed original research from the first tier, meaning the Specialty Journals, are effectively electronically nominated by the article tracking numbers to write a “tier 2” article on the same subject, but geared toward a broader audience and thus placing the findings in a broader context. This Focused Review would be published on the general Frontiers in Immunology site, and not in a specialty section. The Reviewers and Editor of this prestigious article are then also invited to submit a Frontiers Commentary on the article, which is also featured in Frontiers in Immunology. In other words, the whole community of scientific peers – rather than the publisher's editorial staff – democratically selects the highest quality papers for recognition based on actual readership. The quality of a Frontiers paper is also ensured by the policies of the construction of the manuscript, as “space” is no longer limited. SOM is kept to a minimum and consists of material that should be in an appendix, such as equations or nucleotide sequence data, and not simply additional text, data, and figures. This allows the authors to place all relevant data and figures in the main body of the paper, so that the reader can easily access and understand the figures, as well as the text. Accordingly, it is the authors’ care in telling a full story and their creativity in the construction of the figures/tables illustrating it that earn recognition, and not simply what prestigious high impact journal in which the final paper appears. For all of these reasons, publishing in Frontiers in Immunology promises to be an enjoyable and useful experience for authors. Ever since scientific publishing began in the seventeenth century, we have been at the mercy of the publishers. Like Rock and Roll artists, we have written the songs and sung the songs, but then we have given up ownership of our creative efforts to the record companies, which have controlled their distribution. Moreover, the traditional publishing companies have charged us for publishing our songs, as well the readers, and then walked away with the proceeds! No more! Frontiers authors retain the copyright to their own work. Just like Steve Jobs revolutionized the music industry with the iPod and iTunes, publishing with Frontiers promises to revolutionize scientific communication!
                Bookmark

                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Writing – original draft
                Role: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: SupervisionRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: Project administrationRole: SoftwareRole: SupervisionRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: VisualizationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                6 December 2018
                December 2018
                14 December 2018
                : 12
                : 12
                : e0006803
                Affiliations
                [1 ] Zeeman Institute, University of Warwick, Coventry, United Kingdom
                [2 ] School of Life Sciences, University of Warwick, Coventry, United Kingdom
                [3 ] Centre for Mathematical Modelling of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
                [4 ] School of Biological Sciences, University of Edinburgh, Edinbugh, United Kingdom
                [5 ] Liverpool School of Tropical Medicine, Liverpool, United Kingdom
                [6 ] Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America
                [7 ] Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom
                Institut Pasteur, FRANCE
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0001-7727-7102
                http://orcid.org/0000-0002-5740-9734
                Article
                PNTD-D-18-00470
                10.1371/journal.pntd.0006803
                6283524
                30521526
                f8b98372-c977-4856-9d94-386080ba1741
                © 2018 Chapman et al

                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.

                History
                : 30 March 2018
                : 30 August 2018
                Page count
                Figures: 5, Tables: 4, Pages: 24
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000865, Bill and Melinda Gates Foundation;
                Award ID: OPP1053230
                Award Recipient :
                This study was supported by the Bill and Melinda Gates Foundation ( https://www.gatesfoundation.org/) in partnership with the Task Force for Global Health ( https://www.taskforce.org/) through the NTD Modelling Consortium [OPP1053230] (LACC, GFM, TDH). The views, opinions, assumptions or any other information set out in this article are solely those of the authors and should not be attributed to the funders or any person connected with the funders. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Tropical Diseases
                Neglected Tropical Diseases
                Leishmaniasis
                Medicine and Health Sciences
                Parasitic Diseases
                Protozoan Infections
                Leishmaniasis
                Medicine and Health Sciences
                Infectious Diseases
                Zoonoses
                Leishmaniasis
                Medicine and Health Sciences
                Diagnostic Medicine
                Medicine and Health Sciences
                Parasitic Diseases
                Research and Analysis Methods
                Immunologic Techniques
                Immunoassays
                Enzyme-Linked Immunoassays
                People and Places
                Population Groupings
                Age Groups
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Serology
                Biology and Life Sciences
                Organisms
                Eukaryota
                Protozoans
                Parasitic Protozoans
                Leishmania
                Leishmania Donovani
                Biology and Life Sciences
                Physiology
                Immune Physiology
                Antibodies
                Medicine and Health Sciences
                Physiology
                Immune Physiology
                Antibodies
                Biology and Life Sciences
                Immunology
                Immune System Proteins
                Antibodies
                Medicine and Health Sciences
                Immunology
                Immune System Proteins
                Antibodies
                Biology and Life Sciences
                Biochemistry
                Proteins
                Immune System Proteins
                Antibodies
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

                Comments

                Comment on this article