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      Relationship between Non-Hodgkin’s lymphoma and blood levels of Epstein-Barr Virus in children in north-western Tanzania: a case control study

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          Abstract

          Background

          Non-Hodgkin’s Lymphomas (NHL) are common in African children, with endemic Burkitt’s lymphoma (BL) being the most common subtype. While the role of Epstein-Barr Virus (EBV) in endemic BL is known, no data are available about clinical presentations of NHL subtypes and their relationship to Human Immunodeficiency Virus (HIV) infection and Epstein Barr Virus (EBV) load in peripheral blood of children in north-western, Tanzania.

          Methods

          A matched case control study of NHL subtypes was performed in children under 15 years of age and their respective controls admitted to Bugando Medical Centre, Sengerema and Shirati district designated hospitals in north-western, Tanzania, between September 2010 and April 2011. Peripheral blood samples were collected on Whatman 903 filter papers and EBV DNA levels were estimated by multiplex real-time PCR. Clinical and laboratory data were collected using a structured data collection tool and analysed using chi-square, Fisher and Wilcoxon rank sum tests where appropriate. The association between NHL and detection of EBV in peripheral blood was assessed using conditional logistic regression model and presented as odds ratios (OR) and 95% confidence intervals (CI).

          Results

          A total of 35 NHL cases and 70 controls matched for age and sex were enrolled. Of NHLs, 32 had BL with equal distribution between jaw and abdominal tumour, 2 had large B cell lymphoma (DLBCL) and 1 had NHL-not otherwise specified (NHL-NOS). Central nervous system (CNS) presentation occurred only in 1 BL patient; 19 NHLs had stage I and II of disease. Only 1 NHL was found to be HIV-seropositive. Twenty-one of 35 (60%) NHL and 21 of 70 (30%) controls had detectable EBV in peripheral blood (OR = 4.77, 95% CI 1.71 – 13.33, p = 0.003). In addition, levels of EBV in blood were significantly higher in NHL cases than in controls (p = 0.024).

          Conclusions

          BL is the most common childhood NHL subtype in north-western Tanzania. NHLs are not associated with HIV infection, but are strongly associated with EBV load in peripheral blood. The findings suggest that high levels of EBV in blood might have diagnostic and prognostic relevance in African children.

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          Most cited references30

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          High-Resolution Labeling and Functional Manipulation of Specific Neuron Types in Mouse Brain by Cre-Activated Viral Gene Expression

          Sandra Kuhlman, Z. Josh Huang (2008)
          We describe a method that combines Cre-recombinase knockin mice and viral-mediated gene transfer to genetically label and functionally manipulate specific neuron types in the mouse brain. We engineered adeno-associated viruses (AAVs) that express GFP, dsRedExpress, or channelrhodopsin (ChR2) upon Cre/loxP recombination-mediated removal of a transcription-translation STOP cassette. Fluorescent labeling was sufficient to visualize neuronal structures with synaptic resolution in vivo, and ChR2 expression allowed light activation of neuronal spiking. The structural dynamics of a specific class of neocortical neuron, the parvalbumin-containing (Pv) fast-spiking GABAergic interneuron, was monitored over the course of a week. We found that although the majority of Pv axonal boutons were stable in young adults, bouton additions and subtractions on axonal shafts were readily observed at a rate of 10.10% and 9.47%, respectively, over 7 days. Our results indicate that Pv inhibitory circuits maintain the potential for structural re-wiring in post-adolescent cortex. With the generation of an increasing number of Cre knockin mice and because viral transfection can be delivered to defined brain regions at defined developmental stages, this strategy represents a general method to systematically visualize the structure and manipulate the function of different cell types in the mouse brain.
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            Non-Hodgkin's lymphoma in childhood.

            John T. Sandlund, W Crist, J Downing (1996)
            Article 0 comments Cited 39 times – based on 0 reviews     Review now
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              Incidence and geographic distribution of endemic Burkitt lymphoma in northern Uganda revisited.

              M Ogwang, Robert Biggar, Sam M Mbulaiteye … (2008)
              Endemic Burkitt lymphoma (BL) is etiologically associated with Epstein-Barr virus and ecologically linked to Plasmodium falciparum malaria. However, these infections imperfectly correlate with BL epidemiology. To obtain recent epidemiological data, we studied district- and county-specific BL incidence and standardized incidence ratios using data collected from 1997 to 2006 at Lacor Hospital in northern Uganda, where studies were last done more than 30 years ago. Among 500 patients, median age was 6 years (interquartile range 5-8) and male-to-female ratio was 1.8:1. Among those known, most presented with abdominal (56%, M:F 1.4:1) vs. only facial tumors (35%, M:F 3.0:1). Abdominal tumors occurred in older (mean age: 7.0 vs. 6.0 years; p < 0.001) and more frequently in female children (68% vs. 50%; OR 2.2, 95% CI 1.5-3.5). The age-standardized incidence was 2.4 per 100,000, being 0.6 in 1-4 year olds, 4.1 in 5-9 year olds and 2.8 in 10-14 year olds and varied 3- to 4-fold across districts. The incidence was lower in districts that were far from Lacor and higher in districts that were close to Lacor. Although districts close to Lacor were also more urbanized, the incidence was higher in the nearby perirural areas. We highlight high-BL incidence and geographic variation in neighboring districts in northern Uganda. Although distance from Lacor clearly influenced the patterns, the incidence was lower in municipal than in surrounding rural areas. Jaw tumors were characterized by young age and male gender, but presentation has shifted away from facial to mostly abdominal. (c) 2008 Wiley-Liss, Inc.
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                Author and article information

                Journal
                Journal ID (nlm-ta): BMC Pediatr
                Journal ID (iso-abbrev): BMC Pediatr
                Title: BMC Pediatrics
                Publisher: BioMed Central
                ISSN (Electronic): 1471-2431
                Publication date Collection: 2013
                Publication date (Electronic): 7 January 2013
                Volume: 13
                Page: 4
                Affiliations
                [1 ]Department of Pediatrics and Child Health, Bugando Medical Centre, P.O. Box 1370, , Mwanza, Tanzania
                [2 ]Department of Oncology, Bugando Medical Centre, P.O. Box 1370, , Mwanza, Tanzania
                [3 ]Department of Pathology, Catholic University of Health and Allied Sciences – Bugando, P.O. Box 1464, , Mwanza, Tanzania
                [4 ]Department of Biochemistry and Molecular Biology, Catholic University of Health and Allied Sciences – Bugando, P.O. Box 1464, , Mwanza, Tanzania
                [5 ]Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology, University of Padova, Unit of Viral Oncology, IOV-IRCCS, Via Gattamelata 64, 35128, Padova, Italy
                Article
                Publisher ID: 1471-2431-13-4
                DOI: 10.1186/1471-2431-13-4
                PMC ID: 3547779
                PubMed ID: 23294539
                SO-VID: 2b34ce7f-999b-4fe5-80a9-d7852fc32595
                Copyright © Copyright ©2013 Kabyemera et al.; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 12 July 2012
                Date accepted : 2 January 2013
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Pediatrics
                Keywords: children,ebv,hiv,non-hodgkin’s lymphoma
                Data availability:
                ScienceOpen disciplines: Pediatrics
                Keywords: children, ebv, hiv, non-hodgkin’s lymphoma

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