<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article
  PUBLIC "-//NLM//DTD Journal Publishing DTD v3.0 20080202//EN" "http://dtd.nlm.nih.gov/publishing/3.0/journalpublishing3.dtd">
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="3.0" xml:lang="en">
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">PLoS Negl Trop Dis</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plosntds</journal-id><journal-title-group>
<journal-title>PLoS Neglected Tropical Diseases</journal-title></journal-title-group>
<issn pub-type="epub">1935-2735</issn>
<publisher>
<publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, USA</publisher-loc></publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">PNTD-D-14-00812</article-id>
<article-id pub-id-type="doi">10.1371/journal.pntd.0003116</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine and health sciences</subject><subj-group><subject>Infectious diseases</subject><subj-group><subject>Infectious disease control</subject></subj-group></subj-group><subj-group><subject>Parasitic diseases</subject><subj-group><subject>Helminth infections</subject><subj-group><subject>Larva migrans</subject><subj-group><subject>Toxocariasis</subject></subj-group></subj-group></subj-group><subj-group><subject>Nematode infections</subject><subject>Parasitic intestinal diseases</subject></subj-group></subj-group></subj-group></article-categories>
<title-group>
<article-title>Toxocariasis in North America: A Systematic Review</article-title>
<alt-title alt-title-type="running-head">Toxocariasis in North America: A Systematic Review</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" equal-contrib="yes" xlink:type="simple"><name name-style="western"><surname>Lee</surname><given-names>Rachel M.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib>
<contrib contrib-type="author" equal-contrib="yes" xlink:type="simple"><name name-style="western"><surname>Moore</surname><given-names>Laura B.</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib>
<contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Bottazzi</surname><given-names>Maria Elena</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib>
<contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Hotez</surname><given-names>Peter J.</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="aff" rid="aff4"><sup>4</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib>
</contrib-group>
<aff id="aff1"><label>1</label><addr-line>Baylor College of Medicine, Houston, Texas, United States of America</addr-line></aff>
<aff id="aff2"><label>2</label><addr-line>James A. Baker Institute of Public Policy, Rice University, Houston, Texas, United States of America</addr-line></aff>
<aff id="aff3"><label>3</label><addr-line>Departments of Medicine, Pediatrics, and Molecular Virology and Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of America</addr-line></aff>
<aff id="aff4"><label>4</label><addr-line>Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Houston, Texas, United States of America</addr-line></aff>
<contrib-group>
<contrib contrib-type="editor" xlink:type="simple"><name name-style="western"><surname>Gasser</surname><given-names>Robin B.</given-names></name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"/></contrib>
</contrib-group>
<aff id="edit1"><addr-line>University of Melbourne, Australia</addr-line></aff>
<author-notes>
<corresp id="cor1">* E-mail: <email xlink:type="simple">hotez@bcm.edu</email></corresp>
<fn fn-type="conflict"><p>The authors have declared that no competing interests exist.</p></fn>
<fn fn-type="con"><p>Analyzed the data: RML LBM MEB PJH. Contributed to the writing of the manuscript: PJH RML LBM. Reviewed and finalized the manuscript: RML LBM MEB PJH.</p></fn>
</author-notes>
<pub-date pub-type="collection"><month>8</month><year>2014</year></pub-date>
<pub-date pub-type="epub"><day>28</day><month>8</month><year>2014</year></pub-date>
<volume>8</volume>
<issue>8</issue>
<elocation-id>e3116</elocation-id>
<history>
<date date-type="received"><day>13</day><month>5</month><year>2014</year></date>
<date date-type="accepted"><day>14</day><month>7</month><year>2014</year></date>
</history>
<permissions>
<copyright-year>2014</copyright-year>
<copyright-holder>Lee et al</copyright-holder><license xlink:type="simple"><license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/" xlink:type="simple">Creative Commons Attribution License</ext-link>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions>
<abstract>
<p>Toxocariasis is an important neglected tropical disease that can manifest as visceral or ocular larva migrans, or covert toxocariasis. All three forms pose a public health problem and cause significant morbidity in areas of high prevalence. To determine the burden of toxocariasis in North America, we conducted a systematic review of the literature following PRISMA guidelines. We found 18 articles with original prevalence, incidence, or case data for toxocariasis. Prevalence estimates ranged from 0.6% in a Canadian Inuit community to 30.8% in Mexican children with asthma. Commonly cited risk factors included: African-American race, poverty, male sex, and pet ownership or environmental contamination by animal feces. Increased prevalence of <italic>Toxocara spp.</italic> infection was linked in a group of case control studies conducted in Mexico to several high risk groups including waste pickers, asthmatic children, and inpatient psychiatry patients. Further research is needed to determine the true current burden of toxocariasis in North America; however the prevalence estimates gathered in this review suggest that the burden of disease is significant.</p>
</abstract>
<abstract abstract-type="summary"><title>Author Summary</title>
<p>Toxocariasis is a parasitic worm infection that is transmitted by the ingestion of parasite eggs present in the feces of dogs and cats. After ingestion of the Toxocara eggs, the released larvae migrate through human organs, including the lungs, liver, brain, and eyes, where they cause inflammation and organ damage. The different larval migrans syndromes associated with toxocariasis are diagnosed by detecting Toxocara antibodies in sera of infected individuals. This study is a systematic review to in order assess the prevalence of toxocariasis in North America and whether selected groups are at risk for infection. The prevalence was highest among Mexican children with asthma, but also African Americans living in poverty exhibited high rates of infection. Among the major risk factors for infection were African-American ethnicity, male sex, pet ownership, and environmental contamination by animal species. Additional high risk groups in Mexico included waste pickers, asthmatic children, and inpatient psychiatry patients. Further research is needed to determine the true current burden of toxocariasis in North America; however, the prevalence estimates gathered in this review suggest that the burden of disease is significant. Thus, toxocariasis may be emerging as an important health disparity in North America</p>
</abstract>
<funding-group><funding-statement>The authors received no specific funding for this work.</funding-statement></funding-group><counts><page-count count="7"/></counts><custom-meta-group><custom-meta id="data-availability" xlink:type="simple"><meta-name>Data Availability</meta-name><meta-value>The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files.</meta-value></custom-meta></custom-meta-group></article-meta>
</front>
<body><sec id="s1">
<title>Introduction</title>
<p>Toxocariasis is an important neglected tropical disease caused by the roundworms <italic>Toxocara canis</italic> and <italic>Toxocara cati</italic>, which are transmitted when eggs in canine or feline feces, respectively, are ingested by humans <xref ref-type="bibr" rid="pntd.0003116-Global1">[1]</xref>. Larvae penetrate the walls of the intestine then travel through the circulatory system to various organs throughout the body. <italic>Toxocara spp.</italic> do not multiply within the human host, but exist in host tissues in a state of arrested development <xref ref-type="bibr" rid="pntd.0003116-Clinton1">[2]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Jones1">[3]</xref>. When larvae die, the inflammatory reaction produced by the body causes the symptoms of toxocariasis <xref ref-type="bibr" rid="pntd.0003116-Global1">[1]</xref>. Toxocariasis can manifest in three ways; visceral larva migrans results from larvae migrating to major organs including the brain, lungs, and liver, causing a variety of signs and symptoms (usually in young children) including eosinophilia, abdominal pain, headache, cognitive and behavioral disturbances, pneumonitis, hepatitis with hepatomegaly, while ocular toxocariasis more commonly occurs in older children and results from larvae migrating to the eye and can cause irreversible vision loss due to scarring of the retina or retinal detachment. Covert toxocariasis, the most difficult form to diagnose, is believed to be caused by chronic exposure and can manifest as eosinophilia with cognitive disturbances, or nonspecific symptoms that resemble asthma, i.e., coughing, and wheezing <xref ref-type="bibr" rid="pntd.0003116-Global1">[1]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Clinton1">[2]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Barry1">[4]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Hotez1">[5]</xref>. Both visceral larva migrans and covert toxocariasis, and often ocular larva migrans, are associated with enzyme immunoassay antibody titers that can remain elevated for months or years <xref ref-type="bibr" rid="pntd.0003116-Woodhall1">[6]</xref>.</p>
<p>Toxocariasis causes significant morbidity and loss of productivity and poses an important, yet largely unaddressed public health problem in areas of high prevalence. Most notably, infection with <italic>Toxocara spp.</italic> has been associated with reduced cognitive function in children; Walsh and colleagues found that infected children scored significantly lower on math, reading, digit span, and block design tests than uninfected children <xref ref-type="bibr" rid="pntd.0003116-Walsh1">[7]</xref>. Infected children were significantly more likely to be in a lower socioeconomic class than uninfected children, though the difference in performance persisted when socioeconomic class was controlled for, suggesting that toxocariasis, like many other neglected tropical diseases, may play a role in perpetuating poverty and contribute to health disparities in endemic areas <xref ref-type="bibr" rid="pntd.0003116-Walsh1">[7]</xref>. It has been suggested that toxocariasis may even partially account for the achievement gap noted among socioeconomically disadvantaged students <xref ref-type="bibr" rid="pntd.0003116-Hotez2">[8]</xref>. Medically, toxocariasis has also been proposed to be a potential cause of asthma, has been associated with seizures, and is an important cause of blindness <xref ref-type="bibr" rid="pntd.0003116-Barry1">[4]</xref>, <xref ref-type="bibr" rid="pntd.0003116-MunozGuzman1">[9]</xref>.</p>
<p>The current burden of disease due to toxocaraisis in North America is largely unknown. We conducted this review in order to determine the both the prevalence of and the amount of available data measuring the burden of toxocariasis in North America, and to identify needed areas of future research.</p>
</sec><sec id="s2" sec-type="methods">
<title>Methods</title>
<sec id="s2a">
<title>Search strategy and selection criteria</title>
<p>Searches were completed in February 2014 using PubMed and were restricted to English articles, articles published in the last 10 years, and articles pertaining to humans. Search terms included “toxocara”, “toxocariasis”, “visceral larva migrans”, and “ocular larva migrans” and the country name: “United States”, “Mexico”, and “Canada”. Searches were also performed using the country names and disease variations as MeSH terms. Non-English articles, dead links, and duplicate results were excluded from abstract review. Abstracts were reviewed by two reviewers and were excluded from full-text review if they were definitively about a different disease or about the relevant disease in an animal population.</p>
</sec><sec id="s2b">
<title>Assessment and data extraction</title>
<p>Documents in the full-text review were classified as containing (1) original prevalence data/estimates for toxocariasis, (2) original incidence or outbreak data, (3) reports of individual cases of toxocariasis, or (4) no original prevalence, incidence, outbreak, or case report information. Citations for unoriginal prevalence, incidence, or case report data were followed up and included in the review if they were English articles published within the past 10 years. Each paper was reviewed independently by two reviewers for figures, tables, or text containing original prevalence, incidence, and case data as well as descriptions of persons or populations affected and reported risk factors for disease. Articles using the same source data but reporting prevalence estimates for different age groups were considered to contain original estimates. Discrepancies between reviewers to resolved by discussion and consensus. This review is compliant with the PRISMA checklist for systematic reviews. Full bibliography available on request.</p>
</sec></sec><sec id="s3">
<title>Results</title>
<p>We found 18 articles with original prevalence, incidence, or case data for toxocariasis (<xref ref-type="fig" rid="pntd-0003116-g001">Figure 1</xref>). Of these articles, 5 reported data in Canada, 8 reported data in the United States, and 5 reported data in Mexico. One article reported only prevalence data, 0 articles reported incidence or outbreak data, 5 articles reported only affected cases, and 12 articles reported both prevalence data and number of affected cases. <xref ref-type="table" rid="pntd-0003116-t001">Table 1</xref> summarizes the prevalence and reported cases data for toxocariasis in North America. 63% (5/8) of articles with seroprevalence estimates for the United States tested blood samples collected during the 1988–1994 National Health and Nutrition Examination Survey (NHANES).</p>
<fig id="pntd-0003116-g001" position="float"><object-id pub-id-type="doi">10.1371/journal.pntd.0003116.g001</object-id><label>Figure 1</label><caption>
<title>Systematic review process.</title>
</caption><graphic mimetype="image" xlink:href="info:doi/10.1371/journal.pntd.0003116.g001" position="float" xlink:type="simple"/></fig><table-wrap id="pntd-0003116-t001" position="float"><object-id pub-id-type="doi">10.1371/journal.pntd.0003116.t001</object-id><label>Table 1</label><caption>
<title>Summary of <italic>Toxocara spp.</italic> seroprevalence estimates in published literature.</title>
</caption><alternatives><graphic id="pntd-0003116-t001-1" position="float" mimetype="image" xlink:href="info:doi/10.1371/journal.pntd.0003116.t001" xlink:type="simple"/>
<table><colgroup span="1"><col align="left" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/></colgroup>
<thead>
<tr>
<td align="left" rowspan="1" colspan="1">Country</td>
<td align="left" rowspan="1" colspan="1">Article</td>
<td align="left" rowspan="1" colspan="1">Year</td>
<td align="left" rowspan="1" colspan="1">Location</td>
<td align="left" rowspan="1" colspan="1">Seroprevalence (IgG)</td>
<td align="left" rowspan="1" colspan="1">N</td>
<td align="left" rowspan="1" colspan="1">Demographics</td>
</tr>
</thead>
<tbody>
<tr>
<td colspan="7" align="left" rowspan="1"><italic>Canada</italic></td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Campagna 2011 <xref ref-type="bibr" rid="pntd.0003116-Campagna1">[26]</xref></td>
<td align="left" rowspan="1" colspan="1">2007</td>
<td align="left" rowspan="1" colspan="1">Eastmain Village, James Bay, Northern Quebec</td>
<td align="left" rowspan="1" colspan="1">5.4%</td>
<td align="left" rowspan="1" colspan="1">6</td>
<td align="left" rowspan="1" colspan="1">Indiginous Cree community, volunteers ages 15 and older, 37% male</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Wemindji Village, James Bay, Northern Quebec</td>
<td align="left" rowspan="1" colspan="1">1.4%</td>
<td align="left" rowspan="1" colspan="1">2</td>
<td align="left" rowspan="1" colspan="1">Indiginous Cree community, volunteers ages 15 and older, 46% male</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Levesque 2007 <xref ref-type="bibr" rid="pntd.0003116-Levesque1">[17]</xref></td>
<td align="left" rowspan="1" colspan="1">2005</td>
<td align="left" rowspan="1" colspan="1">Mistissini Village, Lake Mistissini, Quebec</td>
<td align="left" rowspan="1" colspan="1">4.2%</td>
<td align="left" rowspan="1" colspan="1">2</td>
<td align="left" rowspan="1" colspan="1">Indiginous Cree community, active hunter/trappers and their spouses, 44% male</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Ota 2009 <xref ref-type="bibr" rid="pntd.0003116-Ota1">[27]</xref></td>
<td align="left" rowspan="1" colspan="1">2008</td>
<td align="left" rowspan="1" colspan="1">Alberta</td>
<td align="left" rowspan="1" colspan="1">-</td>
<td align="left" rowspan="1" colspan="1">1</td>
<td align="left" rowspan="1" colspan="1">14 month old boy with history of retinoblastoma</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Sampasa-Kayinga 2012 <xref ref-type="bibr" rid="pntd.0003116-SampasaKanyinga1">[11]</xref></td>
<td align="left" rowspan="1" colspan="1">2008</td>
<td align="left" rowspan="1" colspan="1">Chisasibi Village, James Bay, Northern Quebec</td>
<td align="left" rowspan="1" colspan="1">0.6% (95% CI 0.02–3.4%)</td>
<td align="left" rowspan="1" colspan="1">1</td>
<td align="left" rowspan="1" colspan="1">Indiginous Cree community, volunteers ages 18 and older, 41% male</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Waskaganish Village, James Bay, Northern Quebec</td>
<td align="left" rowspan="1" colspan="1">10% (95% CI 4.9–17.5%)</td>
<td align="left" rowspan="1" colspan="1">10</td>
<td align="left" rowspan="1" colspan="1">Indiginous Cree community, volunteers ages 18 and older, 42% male</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Schurer 2013 <xref ref-type="bibr" rid="pntd.0003116-Schurer1">[12]</xref></td>
<td align="left" rowspan="1" colspan="1">2011</td>
<td align="left" rowspan="1" colspan="1">Saskatchewan</td>
<td align="left" rowspan="1" colspan="1">13.4%</td>
<td align="left" rowspan="1" colspan="1">27</td>
<td align="left" rowspan="1" colspan="1">Indiginous Dene community, volunteers ages 4 and older, 62% male</td>
</tr>
<tr>
<td colspan="7" align="left" rowspan="1"><italic>United States</italic></td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Congdon 2011 <xref ref-type="bibr" rid="pntd.0003116-Congdon1">[16]</xref></td>
<td align="left" rowspan="1" colspan="1">1988–1994</td>
<td align="left" rowspan="1" colspan="1">Countrywide</td>
<td align="left" rowspan="1" colspan="1">14.6% males, 12.6% females</td>
<td align="left" rowspan="1" colspan="1">2862</td>
<td align="left" rowspan="1" colspan="1">NHANES data, adults and children ages 6 and over</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Jones 2008 <xref ref-type="bibr" rid="pntd.0003116-Jones1">[3]</xref></td>
<td align="left" rowspan="1" colspan="1">1988–1994</td>
<td align="left" rowspan="1" colspan="1">Countrywide</td>
<td align="left" rowspan="1" colspan="1">8.6%</td>
<td align="left" rowspan="1" colspan="1">63</td>
<td align="left" rowspan="1" colspan="1">NHANES data, children ages 1–5</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">15.1%</td>
<td align="left" rowspan="1" colspan="1">240</td>
<td align="left" rowspan="1" colspan="1">NHANES data, children ages 6–11</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">MMWR 2011 <xref ref-type="bibr" rid="pntd.0003116-XX1">[15]</xref></td>
<td align="left" rowspan="1" colspan="1">Sept 2009–Sept 2010</td>
<td align="left" rowspan="1" colspan="1">23 states, DC, and Puerto Rico <xref ref-type="table-fn" rid="nt101">*</xref></td>
<td align="left" rowspan="1" colspan="1">-</td>
<td align="left" rowspan="1" colspan="1">68</td>
<td align="left" rowspan="1" colspan="1">Newly diagnosed ocular toxocariasis cases reported by ophthalmologists, median age 8.5 years (range 1–60 years), 56% male</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Stewart 2005 <xref ref-type="bibr" rid="pntd.0003116-Stewart1">[21]</xref></td>
<td align="left" rowspan="1" colspan="1">1977–1996</td>
<td align="left" rowspan="1" colspan="1">San Francisco, California</td>
<td align="left" rowspan="1" colspan="1">-</td>
<td align="left" rowspan="1" colspan="1">22</td>
<td align="left" rowspan="1" colspan="1">Ocular toxocariasis patients seen for uveitits, median age 14 years (range 1–37 years), 45.5% male</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Walsh 2011 <xref ref-type="bibr" rid="pntd.0003116-Walsh2">[19]</xref></td>
<td align="left" rowspan="1" colspan="1">1988–1994</td>
<td align="left" rowspan="1" colspan="1">Countrywide</td>
<td align="left" rowspan="1" colspan="1">14.2% (95% CI 12.7–15.9%)</td>
<td align="left" rowspan="1" colspan="1">1898</td>
<td align="left" rowspan="1" colspan="1">NHANES data, adults age 17–64</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Walsh 2012 <xref ref-type="bibr" rid="pntd.0003116-Walsh1">[7]</xref></td>
<td align="left" rowspan="1" colspan="1">1988–1994</td>
<td align="left" rowspan="1" colspan="1">Countrywide</td>
<td align="left" rowspan="1" colspan="1">-</td>
<td align="left" rowspan="1" colspan="1">688</td>
<td align="left" rowspan="1" colspan="1">NHANES data, children ages 6–16</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Won 2008 <xref ref-type="bibr" rid="pntd.0003116-Won1">[10]</xref></td>
<td align="left" rowspan="1" colspan="1">1988–1994</td>
<td align="left" rowspan="1" colspan="1">Countrywide</td>
<td align="left" rowspan="1" colspan="1">13.9% (95% CI 12.5–15.3%)</td>
<td align="left" rowspan="1" colspan="1">2835</td>
<td align="left" rowspan="1" colspan="1">NHANES data, adults and children over 6 years, 48.4% male</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Woodhall 2012 <xref ref-type="bibr" rid="pntd.0003116-Woodhall2">[20]</xref></td>
<td align="left" rowspan="1" colspan="1">Sept 2009–Sept 2010</td>
<td align="left" rowspan="1" colspan="1">33 states, DC, and Puerto Rico<xref ref-type="table-fn" rid="nt102">**</xref></td>
<td align="left" rowspan="1" colspan="1">-</td>
<td align="left" rowspan="1" colspan="1">159</td>
<td align="left" rowspan="1" colspan="1">Ocular toxocariasis patients reported by ophthalmologists, median age 11.5 years (range 1–66 years), 54% male</td>
</tr>
<tr>
<td colspan="7" align="left" rowspan="1"><italic>Mexico</italic></td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Alvarado-Esquivel 2013 <xref ref-type="bibr" rid="pntd.0003116-AlvaradoEsquivel1">[13]</xref></td>
<td align="left" rowspan="1" colspan="1">-</td>
<td align="left" rowspan="1" colspan="1">Durango City</td>
<td align="left" rowspan="1" colspan="1">13%</td>
<td align="left" rowspan="1" colspan="1">12</td>
<td align="left" rowspan="1" colspan="1">Waste pickers, mean age 36 years (range 14–76 years), 38% male</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Alvarado-Esquivel 2013 <xref ref-type="bibr" rid="pntd.0003116-AlvaradoEsquivel2">[14]</xref></td>
<td align="left" rowspan="1" colspan="1">-</td>
<td align="left" rowspan="1" colspan="1">Durango City</td>
<td align="left" rowspan="1" colspan="1">4.7%</td>
<td align="left" rowspan="1" colspan="1">6</td>
<td align="left" rowspan="1" colspan="1">Inpatient psychiatric patients, mean age 43.6 (range 16–83), 69% e s</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Jimenez-Balderas 2012 <xref ref-type="bibr" rid="pntd.0003116-JimenezBalderas1">[28]</xref></td>
<td align="left" rowspan="1" colspan="1">Mexico City</td>
<td align="left" rowspan="1" colspan="1">16.6%</td>
<td align="left" rowspan="1" colspan="1">4</td>
<td align="left" rowspan="1" colspan="1">Ankylosing spondylitis patients, mean age 44 years, 38% male</td>
<td align="left" rowspan="1" colspan="1"/>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Munoz-Guzman 2010 <xref ref-type="bibr" rid="pntd.0003116-MunozGuzman1">[9]</xref></td>
<td align="left" rowspan="1" colspan="1">-</td>
<td align="left" rowspan="1" colspan="1">Mexico City</td>
<td align="left" rowspan="1" colspan="1">30.80%</td>
<td align="left" rowspan="1" colspan="1">-</td>
<td align="left" rowspan="1" colspan="1">Asthmatic children from the Traumatology Service of Federico Gomez Children's Hospital, mean age 6.9 years (range 4–12 years), 65% male</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Romero Nunez 2013 <xref ref-type="bibr" rid="pntd.0003116-RomeroNunez1">[18]</xref></td>
<td align="left" rowspan="1" colspan="1">Aug 2010–Sept 2010</td>
<td align="left" rowspan="1" colspan="1">Municipality of Ecatepec of Morelos</td>
<td align="left" rowspan="1" colspan="1">22.2%</td>
<td align="left" rowspan="1" colspan="1">26</td>
<td align="left" rowspan="1" colspan="1">Volunteers age 2–16 years, 48% male</td>
</tr>
</tbody>
</table>
</alternatives><table-wrap-foot><fn id="nt101"><label/><p>*Alabama (5), Arkansas (2), California (6), Connecticut (2), District of Columbia (3), Florida (8), Georgia (9), Illinois (3), Indiana (2), Iowa (1), Louisiana (1), Maryland (2), Nevada (2), New York (3), North Carolina (1), Ohio (1), Oklahoma (1), Oregon (1), Pennsylvania (1), Puerto Rico (1), South Carolina (3), Tennessee (1), Texas (16), Virginia (2), West Virginia (1).</p></fn><fn id="nt102"><label/><p>**Alabama (6), Arkansas (2), California (7), Colorado (3), Connecticut (3), District of Columbia (8), Florida (10), Georgia (9), Hawaii (1), Idaho (2), Illinois (13), Indiana (6), Iowa (2), Louisiana (2), Maryland (4), Massachusetts (2), Michigan (2), Minnesota (2), Missouri (1), Nevada (3), New York (14), North Carolina (2), Ohio (10), Oklahoma (5), Oregon (1), Pennsylvania (6), Puerto Rico (1), Rhode Island (1), South Carolina (3), Tennessee (3), Texas (13), Utah (1), Virginia (3), Washington (7), West Virginia (1).</p></fn></table-wrap-foot></table-wrap>
<p>Data for the United States was the most robust, as many articles analyzed blood samples collected for NHANES, which collects data from a population representative of that of the United States. However, blood samples for the most recent NHANES were collected between 1988 and 1994 and thus prevalence data may not be representative of the current burden of disease 20 years later. Prevalence estimates for the United States ranged from 8.6% for ages 1–5 to 15.1% for ages 6–11, with an overall prevalence rate of 13.9% reported for all adults and children ages 6 and older <xref ref-type="bibr" rid="pntd.0003116-Jones1">[3]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Won1">[10]</xref>. Data for Canada focused mainly on indigenous communities living in rural areas. Prevalence estimates ranged from 0.6% to 13.4%, indicating that for some communities toxocara infection causes a significant burden; however, the overall burden of disease in Canada as a whole is still unknown <xref ref-type="bibr" rid="pntd.0003116-SampasaKanyinga1">[11]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Schurer1">[12]</xref>. Reported seroprevalence estimates in Mexico tended to be higher than those reported for the United States and Canada and the data available focused on comparing prevalence rates in high-risk groups, such as psychiatry patients, waste pickers, and asthmatic children to controls (<xref ref-type="table" rid="pntd-0003116-t002">Table 2</xref>) <xref ref-type="bibr" rid="pntd.0003116-MunozGuzman1">[9]</xref>, <xref ref-type="bibr" rid="pntd.0003116-AlvaradoEsquivel1">[13]</xref>, <xref ref-type="bibr" rid="pntd.0003116-AlvaradoEsquivel2">[14]</xref>. Seroprevalence rates in these high-risk groups ranged from 4.7% in inpatient psychiatric patients to 30.8% in children with asthma <xref ref-type="bibr" rid="pntd.0003116-MunozGuzman1">[9]</xref>, <xref ref-type="bibr" rid="pntd.0003116-AlvaradoEsquivel2">[14]</xref>.</p>
<table-wrap id="pntd-0003116-t002" position="float"><object-id pub-id-type="doi">10.1371/journal.pntd.0003116.t002</object-id><label>Table 2</label><caption>
<title>Case control studies of <italic>Toxocara spp.</italic> seroprevalence.</title>
</caption><alternatives><graphic id="pntd-0003116-t002-2" position="float" mimetype="image" xlink:href="info:doi/10.1371/journal.pntd.0003116.t002" xlink:type="simple"/>
<table><colgroup span="1"><col align="left" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/></colgroup>
<thead>
<tr>
<td align="left" rowspan="1" colspan="1">Article</td>
<td align="left" rowspan="1" colspan="1">Case Group</td>
<td align="left" rowspan="1" colspan="1">Case Group Seroprevalence (N)</td>
<td align="left" rowspan="1" colspan="1">Control Group</td>
<td align="left" rowspan="1" colspan="1">Control Group Seroprevalnce (N)</td>
<td align="left" rowspan="1" colspan="1">P value</td>
</tr>
</thead>
<tbody>
<tr>
<td align="left" rowspan="1" colspan="1">Alvarado-Esquivel 2013 <xref ref-type="bibr" rid="pntd.0003116-AlvaradoEsquivel1">[13]</xref></td>
<td align="left" rowspan="1" colspan="1">90 waste pickers aged 14–76 years, 38% male</td>
<td align="left" rowspan="1" colspan="1">13% (12)</td>
<td align="left" rowspan="1" colspan="1">90 non-waste pickers of various occupations matched by age and gender</td>
<td align="left" rowspan="1" colspan="1">1% (1)</td>
<td align="left" rowspan="1" colspan="1">&lt;0.01</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Alvarado-Esquivel 2013 <xref ref-type="bibr" rid="pntd.0003116-AlvaradoEsquivel2">[14]</xref></td>
<td align="left" rowspan="1" colspan="1">128 psychiatric inpatients aged 16–83 years, 69% male</td>
<td align="left" rowspan="1" colspan="1">4.7% (6)</td>
<td align="left" rowspan="1" colspan="1">276 volunteers aged 16–91 years, 40% male</td>
<td align="left" rowspan="1" colspan="1">1.1% (3)</td>
<td align="left" rowspan="1" colspan="1">0.03</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Jimenez-Balderas 2012 <xref ref-type="bibr" rid="pntd.0003116-JimenezBalderas1">[28]</xref></td>
<td align="left" rowspan="1" colspan="1">24 ankylosing spondylitis patients mean age 44±14 years, 38% male</td>
<td align="left" rowspan="1" colspan="1">16.6% (4)</td>
<td align="left" rowspan="1" colspan="1">77 healthy volunteers mean age 30±15 years, 40% male</td>
<td align="left" rowspan="1" colspan="1">2.6% (2)</td>
<td align="left" rowspan="1" colspan="1">0.027</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Munoz-Guzman 2010 <xref ref-type="bibr" rid="pntd.0003116-MunozGuzman1">[9]</xref></td>
<td align="left" rowspan="1" colspan="1">285 asthmatic children aged 4–12 years, 65% male</td>
<td align="left" rowspan="1" colspan="1">30.8% (88)</td>
<td align="left" rowspan="1" colspan="1">152 non-asthmatic children aged 4–12 years</td>
<td align="left" rowspan="1" colspan="1">19.7% (30)</td>
<td align="left" rowspan="1" colspan="1">&lt;0.05</td>
</tr>
</tbody>
</table>
</alternatives><table-wrap-foot><fn id="nt103"><label/><p>All case control studies identified were conducted in Mexico.</p></fn></table-wrap-foot></table-wrap>
<p>The most commonly cited risk factors for toxocariasis included male sex, canine or feline pet ownership, particularly if the animals are allowed to live primarily outdoors and eat other animals or otherwise unconventional pet food, African American race, age less than 18, low level of education, being foreign born, living in the southern United States, and playing at parks or in sandboxes where dogs and cats have defecated (<xref ref-type="fig" rid="pntd-0003116-g002">Figure 2</xref>).</p>
<fig id="pntd-0003116-g002" position="float"><object-id pub-id-type="doi">10.1371/journal.pntd.0003116.g002</object-id><label>Figure 2</label><caption>
<title>Articles citing risk factors for <italic>Toxocara spp.</italic> infection.</title>
</caption><graphic mimetype="image" xlink:href="info:doi/10.1371/journal.pntd.0003116.g002" position="float" xlink:type="simple"/></fig>
<p>Twelve studies reported prevalence of <italic>Toxocara spp.</italic> antibodies by gender <xref ref-type="bibr" rid="pntd.0003116-Clinton1">[2]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Jones1">[3]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Walsh1">[7]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Won1">[10]</xref>, <xref ref-type="bibr" rid="pntd.0003116-SampasaKanyinga1">[11]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Schurer1">[12]</xref>, <xref ref-type="bibr" rid="pntd.0003116-XX1">[15]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Congdon1">[16]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Levesque1">[17]</xref>, <xref ref-type="bibr" rid="pntd.0003116-RomeroNunez1">[18]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Walsh2">[19]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Woodhall2">[20]</xref>. Eight (73%) of these studies found a significantly greater prevalence in males compared to females, while 27% of studies found no significant differences between genders. No studies found females to have significantly higher prevalence of toxocara infection than males. Three studies from Canada reported prevalence by gender; two of these studies reported no significant difference in prevalence between genders and one study reported an increased prevalence in males <xref ref-type="bibr" rid="pntd.0003116-SampasaKanyinga1">[11]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Schurer1">[12]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Levesque1">[17]</xref>. Seven studies from the United States reported prevalence by gender; 7 of these studies reported an increased prevalence in males and one study reported no difference between genders <xref ref-type="bibr" rid="pntd.0003116-Clinton1">[2]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Jones1">[3]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Walsh1">[7]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Won1">[10]</xref>, <xref ref-type="bibr" rid="pntd.0003116-XX1">[15]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Congdon1">[16]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Walsh2">[19]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Woodhall2">[20]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Stewart1">[21]</xref>. One study from Mexico reported prevalence by gender; this study found a significantly higher prevalence in males than females <xref ref-type="bibr" rid="pntd.0003116-RomeroNunez1">[18]</xref>.</p>
<p>Canine and feline ownership is a somewhat controversial yet commonly cited risk factor. Infected cats and dogs pass eggs in feces, which can contaminate their environment and be ingested by humans <xref ref-type="bibr" rid="pntd.0003116-Global1">[1]</xref>. Puppies in particular are commonly infected in utero and must be dewormed after birth <xref ref-type="bibr" rid="pntd.0003116-Global1">[1]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Clinton1">[2]</xref>. Uninfected cats and dogs are at a high risk for becoming infected if they live outside or eat a diet of other animals or otherwise unconventional pet food <xref ref-type="bibr" rid="pntd.0003116-Global1">[1]</xref>. These findings indicate that perhaps ownership itself is not an independent risk factor for toxocariasis, but that type of pet care can increase or decrease the risk of infection. Three studies from Canada indicated that pet ownership was not a risk factor, citing that dogs that are owned are more likely to be dewormed than feral dogs, which are more likely to eat an unconventional diet and live exclusively outside <xref ref-type="bibr" rid="pntd.0003116-SampasaKanyinga1">[11]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Schurer1">[12]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Levesque1">[17]</xref>. Additionally, environmental contamination by infected animals is an important risk factor; contamination rates of up to 40% have been found in urban playgrounds and children who play in public areas that are not kept clear of animal feces are at a higher risk for <italic>Toxocara</italic> infection <xref ref-type="bibr" rid="pntd.0003116-Clinton1">[2]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Woodhall2">[20]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Hotez3">[22]</xref>.</p>
<p>All eight studies included in this review from the United States provided prevalence estimates by race. Five of these studies cited African American race as a risk factor <xref ref-type="bibr" rid="pntd.0003116-Jones1">[3]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Walsh1">[7]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Won1">[10]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Congdon1">[16]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Walsh2">[19]</xref>. Jones and colleagues found the odds ratio of Non-Hispanic Blacks being infected compared to Non-Hispanic Whites to be 1.7 (95% CI 1.4–2.0), while the odds ratio for Mexican-Americans compared to white was found to be 0.6 (95% CI 0.4–0.6) <xref ref-type="bibr" rid="pntd.0003116-Jones1">[3]</xref>. The national seroprevalence for ages 6 and over was estimated to be 22.8% in African Americans, 12.6% in Mexican-Americans, and 10.6% in Whites using the 1988–1994 NHANES data <xref ref-type="bibr" rid="pntd.0003116-Won1">[10]</xref>. This disparity in prevalence between races has interesting public health implications. Hotez et al. estimated that as many as 2.8 million African-Americans living in poverty in the United States were infected with <italic>Toxocara spp.</italic> making toxocariasis one of the most common infections in an underrepresented minority group <xref ref-type="bibr" rid="pntd.0003116-Hotez4">[23]</xref>. The three studies that reported an increased prevalence of toxocariasis in Whites compared to African-Americans were studies that involved surveying clinicians treating patients with uveitis and asking them to report cases presented with ocular toxocariasis <xref ref-type="bibr" rid="pntd.0003116-XX1">[15]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Woodhall2">[20]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Stewart1">[21]</xref>. The discrepancy between these two sets of studies may point to an issue of access to healthcare in the African-American community.</p>
</sec><sec id="s4">
<title>Discussion</title>
<p>The findings in this review indicate that the seroprevalence of human toxocariasis is high in North America, frequently exceeding 10 percent in the United States and Mexico and among some populations in Canada. Moreover, they suggest that toxocariasis may be emerging as a North American health disparity, with the highest seroprevalence found among African Americans and children in the southern U.S. and some indigenous communities in Canada, as well as populations with low education levels those living in areas where dog feces are found, indicative of environmental degradation.</p>
<p>The detection of antibodies against Toxocara antigens in sera is associated with past exposure to <italic>T. canis</italic> and <italic>T. cati</italic> eggs and the resulting parasite larval migrations. However, because Toxocara larvae can remain in a developmentally arrested state and live with minimal metabolic activity in mammalian tissues for years <xref ref-type="bibr" rid="pntd.0003116-Loukas1">[24]</xref>, seropositivity – enzyme immunoassay titers can remain positive for years <xref ref-type="bibr" rid="pntd.0003116-Woodhall1">[6]</xref> - may also be indicative of active infection. This finding can help explain the associations noted in case-control studies conducted in Mexico between Toxocara seropositivity and conditions such as asthma and ankylosing spondylitis, and psychiatric illness <xref ref-type="bibr" rid="pntd.0003116-Walsh1">[7]</xref>, <xref ref-type="bibr" rid="pntd.0003116-SampasaKanyinga1">[11]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Schurer1">[12]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Loukas1">[24]</xref>, and US NHANES data linking toxocariasis to pulmonary disease and cognitive deficits <xref ref-type="bibr" rid="pntd.0003116-Woodhall1">[6]</xref>, <xref ref-type="bibr" rid="pntd.0003116-Levesque1">[17]</xref>.</p>
<p>Limitations of this study include restrictions used in our search methodology, in particular only including articles published within the past 10 years. An additional limitation was that the studies conducted in the US mostly relied on the same NHANES data. Another was the lack of harmonization of study populations between the different North American countries. For example all of the Canadian studies were conducted in adults only.</p>
<p>Our overall purpose was to assess the available literature on the current burden of disease and to discern the amount of evidence available to inform current or future public health measures to control and prevent toxocariasis. Ultimately, more recent and widespread research is needed to determine the true current burden of toxocariasis in North America, but the prevalence estimates gathered during this review preliminarily indicate that the burden of disease is not insignificant. Other particularly salient points identified by this review that would benefit from further research efforts include differences in prevalence by race in the United States, especially with how these differences are confounded by or related to income and education levels, the relationship between toxocariasis and asthma in children and between toxocariasis and psychiatric diagnoses in both children and adults, and the cognitive effects of toxocara infection in childhood. Links between arthritis and toxocariasis also require further investigation.</p>
<p>Recently the US Centers for Disease Control and Prevention (CDC) announced an initiative to prioritize five neglected parasitic infections in the US, including toxocariasis <xref ref-type="bibr" rid="pntd.0003116-Parise1">[25]</xref>. Among the major priorities outlined by the CDC are efforts to better define risk factors, and research to elucidate the natural history of toxocariasis and its provocative associations with pulmonary and neurologic diseases <xref ref-type="bibr" rid="pntd.0003116-Woodhall1">[6]</xref>. There is also urgency to develop improved and more widely accessible diagnostic tests for detecting active infection, and studies to optimize current treatment regimens using anthelminthic drugs <xref ref-type="bibr" rid="pntd.0003116-Woodhall1">[6]</xref>. Thus, we are still in the nascent stages of understanding the full extent of human toxocariasis in the US and North America and how to best diagnose, manage and treat, and ultimately prevent this illness and emerging health disparity.</p>
</sec><sec id="s5">
<title>Supporting Information</title>
<supplementary-material id="pntd.0003116.s001" mimetype="application/msword" xlink:href="info:doi/10.1371/journal.pntd.0003116.s001" position="float" xlink:type="simple"><label>Text S1</label><caption>
<p><bold>PRISMA checklist.</bold></p>
<p>(DOC)</p>
</caption></supplementary-material><supplementary-material id="pntd.0003116.s002" mimetype="application/msword" xlink:href="info:doi/10.1371/journal.pntd.0003116.s002" position="float" xlink:type="simple"><label>Text S2</label><caption>
<p><bold>PRISMA flowchart.</bold></p>
<p>(DOC)</p>
</caption></supplementary-material><supplementary-material id="pntd.0003116.s003" mimetype="application/vnd.openxmlformats-officedocument.spreadsheetml.sheet" xlink:href="info:doi/10.1371/journal.pntd.0003116.s003" position="float" xlink:type="simple"><label>Text S3</label><caption>
<p><bold>Full reference list.</bold></p>
<p>(XLSX)</p>
</caption></supplementary-material></sec></body>
<back><ref-list>
<title>References</title>
<ref id="pntd.0003116-Global1"><label>1</label>
<mixed-citation publication-type="book" xlink:type="simple">Global Health - Division of Parasitic Diseases and Malaria (2013) Parasites - Toxocariasis (also known as Roundworm Infection). Atlanta, GA: Centers for Disease Control and Prevention.</mixed-citation>
</ref>
<ref id="pntd.0003116-Clinton1"><label>2</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Clinton</surname><given-names>RM</given-names></name>, <name name-style="western"><surname>Carabin</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Little</surname><given-names>SE</given-names></name> (<year>2010</year>) <article-title>Emerging zoonoses in the southern United States: toxocariasis, bovine tuberculosis and southern tick-associated rash illness</article-title>. <source>The American journal of the medical sciences</source> <volume>340</volume>: <fpage>187</fpage>–<lpage>193</lpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-Jones1"><label>3</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Jones</surname><given-names>JL</given-names></name>, <name name-style="western"><surname>Kruszon-Moran</surname><given-names>D</given-names></name>, <name name-style="western"><surname>Won</surname><given-names>K</given-names></name>, <name name-style="western"><surname>Wilson</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Schantz</surname><given-names>PM</given-names></name> (<year>2008</year>) <article-title>Toxoplasma gondii and Toxocara spp. co-infection</article-title>. <source>The American journal of tropical medicine and hygiene</source> <volume>78</volume>: <fpage>35</fpage>–<lpage>39</lpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-Barry1"><label>4</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Barry</surname><given-names>MA</given-names></name>, <name name-style="western"><surname>Weatherhead</surname><given-names>JE</given-names></name>, <name name-style="western"><surname>Hotez</surname><given-names>PJ</given-names></name>, <name name-style="western"><surname>Woc-Colburn</surname><given-names>L</given-names></name> (<year>2013</year>) <article-title>Childhood parasitic infections endemic to the United States</article-title>. <source>Pediatric clinics of North America</source> <volume>60</volume>: <fpage>471</fpage>–<lpage>485</lpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-Hotez1"><label>5</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Hotez</surname><given-names>PJ</given-names></name> (<year>2008</year>) <article-title>Neglected infections of poverty in the United States of America</article-title>. <source>PLoS neglected tropical diseases</source> <volume>2</volume>: <fpage>e256</fpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-Woodhall1"><label>6</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Woodhall</surname><given-names>DM</given-names></name>, <name name-style="western"><surname>Eberhard</surname><given-names>ML</given-names></name>, <name name-style="western"><surname>Parise</surname><given-names>ME</given-names></name> (<year>2014</year>) <article-title>Review Article: Neglected parasitic infections in the United States: Toxocariasis</article-title>. <source>Am J Trop Med Hyg</source> <volume>90</volume>: <fpage>810</fpage>–<lpage>813</lpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-Walsh1"><label>7</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Walsh</surname><given-names>MG</given-names></name>, <name name-style="western"><surname>Haseeb</surname><given-names>MA</given-names></name> (<year>2012</year>) <article-title>Reduced cognitive function in children with toxocariasis in a nationally representative sample of the United States</article-title>. <source>International journal for parasitology</source> <volume>42</volume>: <fpage>1159</fpage>–<lpage>1163</lpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-Hotez2"><label>8</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Hotez</surname><given-names>PJ</given-names></name> (<year>2014</year>) <article-title>Neglected infections of poverty and the American brain</article-title>. <source>JAMA Psychiatry</source> In press.</mixed-citation>
</ref>
<ref id="pntd.0003116-MunozGuzman1"><label>9</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Munoz-Guzman</surname><given-names>MA</given-names></name>, <name name-style="western"><surname>del Rio-Navarro</surname><given-names>BE</given-names></name>, <name name-style="western"><surname>Valdivia-Anda</surname><given-names>G</given-names></name>, <name name-style="western"><surname>Alba-Hurtado</surname><given-names>F</given-names></name> (<year>2010</year>) <article-title>The increase in seroprevalence to Toxocara canis in asthmatic children is related to cross-reaction with Ascaris suum antigens</article-title>. <source>Allergologia et immunopathologia</source> <volume>38</volume>: <fpage>115</fpage>–<lpage>121</lpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-Won1"><label>10</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Won</surname><given-names>KY</given-names></name>, <name name-style="western"><surname>Kruszon-Moran</surname><given-names>D</given-names></name>, <name name-style="western"><surname>Schantz</surname><given-names>PM</given-names></name>, <name name-style="western"><surname>Jones</surname><given-names>JL</given-names></name> (<year>2008</year>) <article-title>National seroprevalence and risk factors for Zoonotic Toxocara spp. infection</article-title>. <source>The American journal of tropical medicine and hygiene</source> <volume>79</volume>: <fpage>552</fpage>–<lpage>557</lpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-SampasaKanyinga1"><label>11</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Sampasa-Kanyinga</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Levesque</surname><given-names>B</given-names></name>, <name name-style="western"><surname>Anassour-Laouan-Sidi</surname><given-names>E</given-names></name>, <name name-style="western"><surname>Cote</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Serhir</surname><given-names>B</given-names></name>, <etal>et al</etal>. (<year>2012</year>) <article-title>Zoonotic infections in native communities of James Bay, Canada</article-title>. <source>Vector borne and zoonotic diseases</source> <volume>12</volume>: <fpage>473</fpage>–<lpage>481</lpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-Schurer1"><label>12</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Schurer</surname><given-names>JM</given-names></name>, <name name-style="western"><surname>Ndao</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Skinner</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Irvine</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Elmore</surname><given-names>SA</given-names></name>, <etal>et al</etal>. (<year>2013</year>) <article-title>Parasitic zoonoses: one health surveillance in northern Saskatchewan</article-title>. <source>PLoS neglected tropical diseases</source> <volume>7</volume>: <fpage>e2141</fpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-AlvaradoEsquivel1"><label>13</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Alvarado-Esquivel</surname><given-names>C</given-names></name> (<year>2013</year>) <article-title>Toxocariasis in waste pickers: a case control seroprevalence study</article-title>. <source>PloS one</source> <volume>8</volume>: <fpage>e54897</fpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-AlvaradoEsquivel2"><label>14</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Alvarado-Esquivel</surname><given-names>C</given-names></name> (<year>2013</year>) <article-title>Toxocara infection in psychiatric inpatients: a case control seroprevalence study</article-title>. <source>PloS one</source> <volume>8</volume>: <fpage>e62606</fpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-XX1"><label>15</label>
<mixed-citation publication-type="journal" xlink:type="simple"><article-title>Ocular toxocariasis–United States, 2009–2010</article-title>. <source>MMWR Morbidity and mortality weekly report</source> <volume>60</volume>: <fpage>734</fpage>–<lpage>736</lpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-Congdon1"><label>16</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Congdon</surname><given-names>P</given-names></name>, <name name-style="western"><surname>Lloyd</surname><given-names>P</given-names></name> (<year>2011</year>) <article-title>Toxocara infection in the United States: the relevance of poverty, geography and demography as risk factors, and implications for estimating county prevalence</article-title>. <source>International journal of public health</source> <volume>56</volume>: <fpage>15</fpage>–<lpage>24</lpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-Levesque1"><label>17</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Levesque</surname><given-names>B</given-names></name>, <name name-style="western"><surname>Messier</surname><given-names>V</given-names></name>, <name name-style="western"><surname>Bonnier-Viger</surname><given-names>Y</given-names></name>, <name name-style="western"><surname>Couillard</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Cote</surname><given-names>S</given-names></name>, <etal>et al</etal>. (<year>2007</year>) <article-title>Seroprevalence of zoonoses in a Cree community (Canada)</article-title>. <source>Diagnostic microbiology and infectious disease</source> <volume>59</volume>: <fpage>283</fpage>–<lpage>286</lpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-RomeroNunez1"><label>18</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Romero Nunez</surname><given-names>C</given-names></name>, <name name-style="western"><surname>Mendoza Martinez</surname><given-names>GD</given-names></name>, <name name-style="western"><surname>Yanez Arteaga</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Ponce Macotela</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Bustamante Montes</surname><given-names>P</given-names></name>, <etal>et al</etal>. (<year>2013</year>) <article-title>Prevalence and risk factors associated with Toxocara canis infection in children</article-title>. <source>TheScientificWorldJournal</source> <volume>2013</volume>: <fpage>572089</fpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-Walsh2"><label>19</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Walsh</surname><given-names>MG</given-names></name> (<year>2011</year>) <article-title>Toxocara infection and diminished lung function in a nationally representative sample from the United States population</article-title>. <source>International journal for parasitology</source> <volume>41</volume>: <fpage>243</fpage>–<lpage>247</lpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-Woodhall2"><label>20</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Woodhall</surname><given-names>D</given-names></name>, <name name-style="western"><surname>Starr</surname><given-names>MC</given-names></name>, <name name-style="western"><surname>Montgomery</surname><given-names>SP</given-names></name>, <name name-style="western"><surname>Jones</surname><given-names>JL</given-names></name>, <name name-style="western"><surname>Lum</surname><given-names>F</given-names></name>, <etal>et al</etal>. (<year>2012</year>) <article-title>Ocular toxocariasis: epidemiologic, anatomic, and therapeutic variations based on a survey of ophthalmic subspecialists</article-title>. <source>Ophthalmology</source> <volume>119</volume>: <fpage>1211</fpage>–<lpage>1217</lpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-Stewart1"><label>21</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Stewart</surname><given-names>JM</given-names></name>, <name name-style="western"><surname>Cubillan</surname><given-names>LD</given-names></name>, <name name-style="western"><surname>Cunningham</surname><given-names>ET</given-names><suffix>Jr</suffix></name> (<year>2005</year>) <article-title>Prevalence, clinical features, and causes of vision loss among patients with ocular toxocariasis</article-title>. <source>Retina</source> <volume>25</volume>: <fpage>1005</fpage>–<lpage>1013</lpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-Hotez3"><label>22</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Hotez</surname><given-names>PJ</given-names></name> (<year>2007</year>) <article-title>Neglected diseases and poverty in “The Other America”: the greatest health disparity in the United States?</article-title> <source>PLoS neglected tropical diseases</source> <volume>1</volume>: <fpage>e149</fpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-Hotez4"><label>23</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Hotez</surname><given-names>PJ</given-names></name>, <name name-style="western"><surname>Wilkins</surname><given-names>PP</given-names></name> (<year>2009</year>) <article-title>Toxocariasis: America's most common neglected infection of poverty and a helminthiasis of global importance?</article-title> <source>PLoS neglected tropical diseases</source> <volume>3</volume>: <fpage>e400</fpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-Loukas1"><label>24</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Loukas</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Maizels</surname><given-names>RM</given-names></name> (<year>1998</year>) <article-title>Cloning and characterisation of a prohibitin gene from infective larvae of the parasitic nematode Toxocara canis</article-title>. <source>DNA sequence : the journal of DNA sequencing and mapping</source> <volume>9</volume>: <fpage>323</fpage>–<lpage>328</lpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-Parise1"><label>25</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Parise</surname><given-names>ME</given-names></name>, <name name-style="western"><surname>Hotez</surname><given-names>PJ</given-names></name>, <name name-style="western"><surname>Slutsker</surname><given-names>L</given-names></name> (<year>2014</year>) <article-title>Neglected parasitic infections in the United States: Needs and opportunities</article-title>. <source>Am J Trop Med Hyg</source> <volume>90</volume>: <fpage>783</fpage>–<lpage>785</lpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-Campagna1"><label>26</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Campagna</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Levesque</surname><given-names>B</given-names></name>, <name name-style="western"><surname>Anassour-Laouan-Sidi</surname><given-names>E</given-names></name>, <name name-style="western"><surname>Cote</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Serhir</surname><given-names>B</given-names></name>, <etal>et al</etal>. (<year>2011</year>) <article-title>Seroprevalence of 10 zoonotic infections in 2 Canadian Cree communities</article-title>. <source>Diagnostic microbiology and infectious disease</source> <volume>70</volume>: <fpage>191</fpage>–<lpage>199</lpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-Ota1"><label>27</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Ota</surname><given-names>KV</given-names></name>, <name name-style="western"><surname>Dimaras</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Heon</surname><given-names>E</given-names></name>, <name name-style="western"><surname>Babyn</surname><given-names>PS</given-names></name>, <name name-style="western"><surname>Yau</surname><given-names>YC</given-names></name>, <etal>et al</etal>. (<year>2009</year>) <article-title>Toxocariasis mimicking liver, lung, and spinal cord metastases from retinoblastoma</article-title>. <source>The Pediatric infectious disease journal</source> <volume>28</volume>: <fpage>252</fpage>–<lpage>254</lpage>.</mixed-citation>
</ref>
<ref id="pntd.0003116-JimenezBalderas1"><label>28</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Jimenez-Balderas</surname><given-names>FJ</given-names></name>, <name name-style="western"><surname>Camargo-Coronel</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Gargia-Jaimes</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Zonana-Nacach</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Alcantara-Anguianoi</surname><given-names>I</given-names></name>, <etal>et al</etal>. (<year>2012</year>) <article-title>A study on parasites in Mexican rheumatic disease patients</article-title>. <source>Journal of the Egyptian Society of Parasitology</source> <volume>42</volume>: <fpage>271</fpage>–<lpage>280</lpage>.</mixed-citation>
</ref>
</ref-list></back>
</article>