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  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">JDERM</journal-id>
      <journal-id journal-id-type="nlm-ta">JMIR Dermatol</journal-id>
      <journal-title>JMIR Dermatology</journal-title>
      <issn pub-type="epub">2562-0959</issn>
      <publisher>
        <publisher-name>JMIR Publications</publisher-name>
        <publisher-loc>Toronto, Canada</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">v5i4e35034</article-id>
      <article-id pub-id-type="pmid">37632891</article-id>
      <article-id pub-id-type="doi">10.2196/35034</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Paper</subject>
        </subj-group>
        <subj-group subj-group-type="article-type">
          <subject>Original Paper</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Worldwide Evolution of Vaccinable and Nonvaccinable Viral Skin Infections: Google Trends Analysis</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Dellavalle</surname>
            <given-names>Robert</given-names>
          </name>
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Sivesind</surname>
            <given-names>Torunn</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Rovetta</surname>
            <given-names>Alessandro</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib id="contrib1" contrib-type="author" corresp="yes">
          <name name-style="western">
            <surname>Simonart</surname>
            <given-names>Thierry</given-names>
          </name>
          <degrees>MD, PhD</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <address>
            <institution>Department of Dermatology</institution>
            <institution>Delta Hospital, Centre Hospitalier Interrégional Edith Cavell</institution>
            <institution>Université Libre de Bruxelles</institution>
            <addr-line>Bd du Triomphe 201</addr-line>
            <addr-line>Brussels, B-1160</addr-line>
            <country>Belgium</country>
            <phone>32 225229304</phone>
            <email>tsimonar@outlook.com</email>
          </address>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0001-6658-7965</ext-link>
        </contrib>
        <contrib id="contrib2" contrib-type="author">
          <name name-style="western">
            <surname>Lam Hoai</surname>
            <given-names>Xuân-Lan</given-names>
          </name>
          <degrees>MD</degrees>
          <xref rid="aff2" ref-type="aff">2</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0001-6007-0666</ext-link>
        </contrib>
        <contrib id="contrib3" contrib-type="author">
          <name name-style="western">
            <surname>de Maertelaer</surname>
            <given-names>Viviane</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff3" ref-type="aff">3</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0001-6722-7267</ext-link>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution>Department of Dermatology</institution>
        <institution>Delta Hospital, Centre Hospitalier Interrégional Edith Cavell</institution>
        <institution>Université Libre de Bruxelles</institution>
        <addr-line>Brussels</addr-line>
        <country>Belgium</country>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution>Department of Dermatology</institution>
        <institution>St Pierre - Brugmann - Hôpital Universitaire des Enfants Reine Fabiola University Hospitals</institution>
        <institution>Université Libre de Bruxelles</institution>
        <addr-line>Brussels</addr-line>
        <country>Belgium</country>
      </aff>
      <aff id="aff3">
        <label>3</label>
        <institution>Department of Biostatistics</institution>
        <institution>Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire</institution>
        <institution>Université Libre de Bruxelles</institution>
        <addr-line>Brussels</addr-line>
        <country>Belgium</country>
      </aff>
      <author-notes>
        <corresp>Corresponding Author: Thierry Simonart <email>tsimonar@outlook.com</email></corresp>
      </author-notes>
      <pub-date pub-type="collection">
        <season>Oct-Dec</season>
        <year>2022</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>4</day>
        <month>10</month>
        <year>2022</year>
      </pub-date>
      <volume>5</volume>
      <issue>4</issue>
      <elocation-id>e35034</elocation-id>
      <history>
        <date date-type="received">
          <day>17</day>
          <month>11</month>
          <year>2021</year>
        </date>
        <date date-type="rev-request">
          <day>4</day>
          <month>7</month>
          <year>2022</year>
        </date>
        <date date-type="rev-recd">
          <day>24</day>
          <month>8</month>
          <year>2022</year>
        </date>
        <date date-type="accepted">
          <day>11</day>
          <month>9</month>
          <year>2022</year>
        </date>
      </history>
      <copyright-statement>©Thierry Simonart, Xuân-Lan Lam Hoai, Viviane de Maertelaer. Originally published in JMIR Dermatology (http://derma.jmir.org), 04.10.2022.</copyright-statement>
      <copyright-year>2022</copyright-year>
      <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/">
        <p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Dermatology, is properly cited. The complete bibliographic information, a link to the original publication on http://derma.jmir.org, as well as this copyright and license information must be included.</p>
      </license>
      <self-uri xlink:href="https://derma.jmir.org/2022/4/e35034" xlink:type="simple"/>
      <abstract>
        <sec sec-type="background">
          <title>Background</title>
          <p>Most common viral skin infections are not reportable conditions. Studying the population dynamics of these viral epidemics using traditional field methods is costly and time-consuming, especially over wide geographical areas.</p>
        </sec>
        <sec sec-type="objective">
          <title>Objective</title>
          <p>This study aimed to explore the evolution, seasonality, and distribution of vaccinable and nonvaccinable viral skin infections through an analysis of Google Trends.</p>
        </sec>
        <sec sec-type="methods">
          <title>Methods</title>
          <p>Worldwide search trends from January 2004 through May 2021 for viral skin infections were extracted from Google Trends, quantified, and analyzed.</p>
        </sec>
        <sec sec-type="results">
          <title>Results</title>
          <p>Time series decomposition showed that the total search term volume for warts; zoster; roseola; measles; hand, foot, and mouth disease (HFMD); varicella; and rubella increased worldwide over the study period, whereas the interest for <italic>Pityriasis rosea</italic> and herpes simplex decreased. Internet searches for HFMD, varicella, and measles exhibited the highest seasonal patterns. The interest for measles and rubella was more pronounced in African countries, whereas the interest for HFMD and roseola was more pronounced in East Asia.</p>
        </sec>
        <sec sec-type="conclusions">
          <title>Conclusions</title>
          <p>Harnessing data generated by web searches may increase the efficacy of traditional surveillance systems and strengthens the suspicion that the incidence of some vaccinable viral skin infections such as varicella, measles, and rubella may be globally increasing, whereas the incidence of common nonvaccinable skin infections remains stable.</p>
        </sec>
      </abstract>
      <kwd-group>
        <kwd>big data</kwd>
        <kwd>infodemiology</kwd>
        <kwd>measles</kwd>
        <kwd>varicella</kwd>
        <kwd>rubella</kwd>
        <kwd>hand</kwd>
        <kwd>foot</kwd>
        <kwd>mouth disease</kwd>
        <kwd>skin infection</kwd>
        <kwd>epidemic</kwd>
        <kwd>wart</kwd>
        <kwd>skin</kwd>
        <kwd>dermatology</kwd>
        <kwd>trend</kwd>
        <kwd>Google search</kwd>
        <kwd>web search</kwd>
        <kwd>surveillance</kwd>
        <kwd>vaccinable</kwd>
        <kwd>incidence</kwd>
        <kwd>viral epidemics</kwd>
        <kwd>distribution</kwd>
        <kwd>measles</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="introduction">
      <title>Introduction</title>
      <p>Viral skin infections are common reasons for consulting health care providers and represent a substantial public health concern throughout the world. Effective vaccines against viral diseases with primary or prominent cutaneous manifestations include those directed against measles and rubella (now commonly used together with a mumps vaccine as the trivalent MMR), human papillomavirus, varicella, and zoster [<xref ref-type="bibr" rid="ref1">1</xref>]. Although vaccination is an effective method of preventing these diseases [<xref ref-type="bibr" rid="ref2">2</xref>,<xref ref-type="bibr" rid="ref3">3</xref>], large-scale epidemiologic data on their evolution and distribution remain scarce. Studying the population dynamics of these viral epidemics using traditional epidemiological methods is costly and time-consuming, especially over wide geographical areas. Moreover, traditional studies may be affected by the underreporting of cases, data quality issues, reporting delays, or even conflicts of interest, resulting in missed opportunities to respond to trends in disease prevalence. Over the last 2 decades, the use of the internet as an initial information source has become almost ubiquitous among the general population. Google Trends is a web-based tracking system by Google that analyzes the popularity of top search queries in the Google search engine across various regions and languages [<xref ref-type="bibr" rid="ref4">4</xref>,<xref ref-type="bibr" rid="ref5">5</xref>]. Since 2004, Google Trends has been increasingly used to explore web-based health-seeking behaviors, offering a new, interesting tool to monitor public attention with regard to specific diseases. The association between the predictive power of Google Trends and the data of official surveillance systems has been studied for a wide range of medical topics, with the conclusion that it can provide useful real-time data about epidemiological surveillance, screening, and treatment options [<xref ref-type="bibr" rid="ref6">6</xref>-<xref ref-type="bibr" rid="ref13">13</xref>]. Previous studies have examined the utility of Google Trends to monitor various infectious diseases such as influenza, tuberculosis, Lyme disease, COVID-19, dengue, genital warts, lice, or scabies [<xref ref-type="bibr" rid="ref6">6</xref>-<xref ref-type="bibr" rid="ref13">13</xref>]. Since the possible resurgence of some viral skin diseases is a growing concern [<xref ref-type="bibr" rid="ref14">14</xref>], we investigated whether Google Trends could reflect possible changes in the epidemiology of cutaneous viral infections.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <sec>
        <title>Google Trends Data</title>
        <p>The data were obtained from Google Trends, a public web-based database and analytics tool of Google Inc [<xref ref-type="bibr" rid="ref4">4</xref>,<xref ref-type="bibr" rid="ref5">5</xref>]. Similar applications of infoveillance in the investigation of health campaign effectiveness have been described previously [<xref ref-type="bibr" rid="ref15">15</xref>-<xref ref-type="bibr" rid="ref17">17</xref>].</p>
        <p>Google Trends generates data and allows the user to compare the relative search volume (RSV) of 2 or more search terms, offering temporal and geographic models based on the specific terms [<xref ref-type="bibr" rid="ref16">16</xref>-<xref ref-type="bibr" rid="ref18">18</xref>]. It shows how often a given search term is entered into the Google search engine relative to the website’s total search volume over a given period of time. Google Trends can be used for comparative keyword research and to discover event-triggered spikes in keyword search volume.</p>
        <p>The RSV is assigned to the search terms. The RSV values represent the goal of the research based on the highest point of the plot with respect to a region or a specific period. The RSV values do not represent absolute search volume numbers but rather normalized values reflected on a scale from 0 to 100, where 100 is the point of maximum popularity among the search terms or topics over a specified time frame. When no sufficient data are found regarding the search term, the score drops to 0 [<xref ref-type="bibr" rid="ref5">5</xref>,<xref ref-type="bibr" rid="ref12">12</xref>,<xref ref-type="bibr" rid="ref13">13</xref>,<xref ref-type="bibr" rid="ref19">19</xref>,<xref ref-type="bibr" rid="ref20">20</xref>]. Relative monthly scores for all search terms and topics are expressed as relative interest scores, which are surrogates for the relative popularity of a particular search term and topic over that time frame.</p>
        <p>The keywords were selected from articles on viral skin diseases or infections [<xref ref-type="bibr" rid="ref21">21</xref>,<xref ref-type="bibr" rid="ref22">22</xref>], and the usual name of the most common diseases were considered.</p>
        <p>A search-term query in Google Trends provides searches for an exact search term, whereas a topic query includes related search terms (in any language, such as German, Portuguese, Chinese, Ukrainian, or Spanish) [<xref ref-type="bibr" rid="ref23">23</xref>]. Google Trends facilitates the easy comparison of the given terms regardless of the language of Google users. We focused our analysis on the “Related Searches” section, which shows queries (and not keywords) that are related to the entered terms (which are instead true keywords). The data were obtained using the following topic queries, in the “Global” category (all available categories in Google Trends were included): “rougeole” (“measles” in French) as the subject; “herpès” (“herpes” in French) as the disease; “varicelle” (“chickenpox” in French) as the disease; “zona” (“zoster” in French) as the subject; “syndrome pieds-mains-bouche” (“hand, foot, and mouth disease” [HFMD] in French) as the disease; “molluscum contagiosum” as the subject; “verrue” (“warts” in French) as the subject; “pytiriasis rosé de Gibert” (“<italic>Pityriasis rosea</italic>” in French) as the disease; “exanthème subit” (“roseola” in French) as the disease; and “rubéole” (“rubella” in French) as the disease. The data were obtained in the time frame elapsing from January 1, 2004, to May 2021 (n=209 months) worldwide and aggregated by month. To compare the temporal evolution of the searches, the file in CSV format for each search was downloaded separately.</p>
      </sec>
      <sec>
        <title>Ethical Considerations</title>
        <p>Ethics approval for this type of study was not required as none of the queries in the Google database can be associated with any identity or physical location, as specified in Google’s privacy policy [<xref ref-type="bibr" rid="ref24">24</xref>].</p>
      </sec>
      <sec>
        <title>Data and Statistical Analysis</title>
        <p>For the entire period (n=209 months), linear adjusted lines of the RSV index representing a normalized value, ranging from 0 (no searches) to 100 (for the peak of the search), were generated separately for several variables of interest. These linear fitted lines visually compared the trends of interest in common viral skin infections over the past 17 years. Seasonality was investigated through decomposition time series multiplicative models [<xref ref-type="bibr" rid="ref25">25</xref>]. They were used with 12 months as the number of seasons on the RSV index (dependent variable). The quality of the model was evaluated through the pseudo <italic>R</italic>-squared for each variable. Seasonality was investigated for each variable. Their amplitudes, quantified as the difference between their highest and lowest monthly coefficients, were compared. Technical details concerning the statistical model and analysis are described in <xref ref-type="supplementary-material" rid="app1">Multimedia Appendix 1</xref>. The statistical software used were SPSS (version 27.0; IBM Corp) and NCSS (version 10; NCSS LLC).</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <p>The temporal evolution for the worldwide 17-year Google Trends data (from January 2004 to May 2021) regarding the variables mentioned under the Methods section is presented in <xref rid="figure1" ref-type="fig">Figure 1</xref>. They were adjusted through linear straight lines showing that the total search term volume for chickenpox, HFMD, measles, molluscum contagiosum<bold>,</bold> roseola, warts, and zoster increased worldwide over the study period, whereas the interest for <italic>Pityriasis rosea</italic> decreased. We found nearly no change (slopes ≤0.022) in interest for molluscum contagiosum (<xref ref-type="table" rid="table1">Table 1</xref>). The quality of the adjustment to the multiplicative model was satisfying.</p>
      <p>Seasonality in worldwide internet searches (reflecting mainly the Northern Hemisphere, since 90% of the world’s population and most of the internet users lives there [<xref ref-type="bibr" rid="ref26">26</xref>,<xref ref-type="bibr" rid="ref27">27</xref>]) was quantified as the difference between the highest and lowest seasonality coefficients, which were in decreasing order as follows: HFMD, chickenpox, measles, molluscum contagiosum, warts, roseola, rubella, <italic>Pityriasis rosea</italic>, zoster, and herpes (<xref ref-type="table" rid="table1">Table 1</xref>). The peaks of interest were in March for <italic>Pityriasis rosea</italic>; April for measles and chickenpox; May for rubella; June for molluscum contagiosum; July for HFMD, roseola, zoster, and warts; and August for herpes and zoster (<xref ref-type="table" rid="table1">Table 1</xref> and <xref rid="figure2" ref-type="fig">Figure 2</xref>).</p>
      <p>The top 5 regions where the queries for measles and rubella were the most popular were exclusively African countries. The top 5 regions where the queries for HFMD and roseola were the most popular were mostly in East Asia (<xref ref-type="table" rid="table2">Table 2</xref>).</p>
      <fig id="figure1" position="float">
        <label>Figure 1</label>
        <caption>
          <p>Data corresponding to searches for chickenpox; herpes; hand, foot, and mouth disease (HFMD); measles; molluscum contagiosum; <italic>Pityriasis rosea</italic>; roseola; rubella; warts; and zoster from Google Trends time data (17 years; 209 months). To compare the temporal evolution of the searches, data for each search were downloaded separately and are presented as a relative search volume (RSV) index. They do not represent absolute search volume numbers but rather a normalized value, ranging from 0 (for no searches) to 100 (for the peak of the search). The linear trends are represented.</p>
        </caption>
        <graphic xlink:href="derma_v5i4e35034_fig1.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
      </fig>
      <table-wrap position="float" id="table1">
        <label>Table 1</label>
        <caption>
          <p>
          Seasonality and trends in worldwide internet searches for varicella, herpes, HFMD, measles, molluscum contagiosum, <italic>Pityriasis rosea</italic>, Roseola, rubella, warts, and zoster.
        </p>
        </caption>
        <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
          <col width="30"/>
          <col width="170"/>
          <col width="80"/>
          <col width="70"/>
          <col width="70"/>
          <col width="90"/>
          <col width="70"/>
          <col width="90"/>
          <col width="80"/>
          <col width="90"/>
          <col width="70"/>
          <col width="90"/>
          <thead>
            <tr valign="top">
              <td colspan="2">
                <break/>
              </td>
              <td>Varicella</td>
              <td>Herpes</td>
              <td>HFMD<sup>a</sup></td>
              <td>Measles</td>
              <td>MC<sup>b</sup></td>
              <td>
                <italic>Pityriasis rosea</italic>
              </td>
              <td>Roseola</td>
              <td>Rubella</td>
              <td>Warts</td>
              <td>Zoster</td>
            </tr>
          </thead>
          <tbody>
            <tr valign="top">
              <td colspan="12">
                <bold>Month, seasonal coefficient (%)</bold>
              </td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>January</td>
              <td>103</td>
              <td>100</td>
              <td>55</td>
              <td>89,8</td>
              <td>93</td>
              <td>103</td>
              <td>85</td>
              <td>91</td>
              <td>92</td>
              <td>97</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>February</td>
              <td>105</td>
              <td>103</td>
              <td>58</td>
              <td>113</td>
              <td>93</td>
              <td>108</td>
              <td>91</td>
              <td>100</td>
              <td>93</td>
              <td>96</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>March</td>
              <td>116</td>
              <td>100</td>
              <td>67</td>
              <td>114</td>
              <td>98</td>
              <td>107</td>
              <td>92</td>
              <td>108</td>
              <td>95</td>
              <td>98</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>April</td>
              <td>118</td>
              <td>100</td>
              <td>82</td>
              <td>123</td>
              <td>106</td>
              <td>105</td>
              <td>105</td>
              <td>113</td>
              <td>101</td>
              <td>100</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>May</td>
              <td>117</td>
              <td>99</td>
              <td>120</td>
              <td>125</td>
              <td>112</td>
              <td>104</td>
              <td>116</td>
              <td>115</td>
              <td>107</td>
              <td>100</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>June</td>
              <td>113</td>
              <td>97</td>
              <td>122</td>
              <td>98</td>
              <td>115</td>
              <td>104</td>
              <td>120</td>
              <td>101</td>
              <td>111</td>
              <td>104</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>July</td>
              <td>95</td>
              <td>103</td>
              <td>156</td>
              <td>84</td>
              <td>113</td>
              <td>94</td>
              <td>124</td>
              <td>92</td>
              <td>116</td>
              <td>105</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>August</td>
              <td>79</td>
              <td>105</td>
              <td>132</td>
              <td>90</td>
              <td>108</td>
              <td>90</td>
              <td>110</td>
              <td>96</td>
              <td>114</td>
              <td>105</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>September</td>
              <td>77</td>
              <td>99</td>
              <td>115</td>
              <td>95</td>
              <td>99</td>
              <td>93</td>
              <td>85</td>
              <td>99</td>
              <td>102</td>
              <td>102</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>October</td>
              <td>84</td>
              <td>98</td>
              <td>116</td>
              <td>90</td>
              <td>91</td>
              <td>97</td>
              <td>91</td>
              <td>102</td>
              <td>94</td>
              <td>101</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>November</td>
              <td>93</td>
              <td>99</td>
              <td>101</td>
              <td>93</td>
              <td>90</td>
              <td>98</td>
              <td>85</td>
              <td>98</td>
              <td>90</td>
              <td>98</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>December</td>
              <td>101</td>
              <td>97</td>
              <td>75</td>
              <td>77</td>
              <td>82</td>
              <td>97</td>
              <td>84</td>
              <td>86</td>
              <td>84</td>
              <td>93</td>
            </tr>
            <tr valign="top">
              <td colspan="2">Delta</td>
              <td>41</td>
              <td>8</td>
              <td>101</td>
              <td>51</td>
              <td>33</td>
              <td>18</td>
              <td>40</td>
              <td>29</td>
              <td>32</td>
              <td>12</td>
            </tr>
            <tr valign="top">
              <td colspan="2">Slope of the adjusted straight lines</td>
              <td>–0.091</td>
              <td>–0.112</td>
              <td>–0.024</td>
              <td>0.015</td>
              <td>–0.146</td>
              <td>–0.121</td>
              <td>0.104</td>
              <td>–0.016</td>
              <td>0.137</td>
              <td>0.099</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="table1fn1">
            <p><sup>a</sup>HFMD: hand, foot, and mouth disease.</p>
          </fn>
          <fn id="table1fn2">
            <p><sup>b</sup>MC: molluscum contagiosum.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <fig id="figure2" position="float">
        <label>Figure 2</label>
        <caption>
          <p>Seasonality coefficients (moving averages) of varicella, HFMD, measles, molluscum contagiosum, and <italic>Pityriasis rosea</italic>. For the clarity of the graph, only the infections with the highest seasonality coefficients are represented. HFMD: hand, foot, and mouth disease; PPGSS: papular-purpuric gloves and socks syndrome.</p>
        </caption>
        <graphic xlink:href="derma_v5i4e35034_fig2.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
      </fig>
      <table-wrap position="float" id="table2">
        <label>Table 2</label>
        <caption>
          <p>Top 5 regions for the queries for HFMD, measles, <italic>Pityriasis rosea</italic>, roseola, and rubella.</p>
        </caption>
        <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
          <col width="250"/>
          <col width="150"/>
          <col width="150"/>
          <col width="150"/>
          <col width="150"/>
          <col width="150"/>
          <thead>
            <tr valign="top">
              <td>Viral skin infection</td>
              <td colspan="5">Region</td>
            </tr>
            <tr valign="top">
              <td>
                <break/>
              </td>
              <td>Rank 1</td>
              <td>Rank 2</td>
              <td>Rank 3</td>
              <td>Rank 4</td>
              <td>Rank 5</td>
            </tr>
          </thead>
          <tbody>
            <tr valign="top">
              <td>HFMD<sup>a</sup></td>
              <td>China</td>
              <td>Singapore</td>
              <td>Vietnam</td>
              <td>Finland</td>
              <td>Hong Kong</td>
            </tr>
            <tr valign="top">
              <td>Measles</td>
              <td>Niger</td>
              <td>Chad</td>
              <td>Congo-Kinshasa</td>
              <td>Madagascar</td>
              <td>Guinea</td>
            </tr>
            <tr valign="top">
              <td>
                <italic>Pityriasis rosea</italic>
              </td>
              <td>Jamaica</td>
              <td>Bulgaria</td>
              <td>Belarus</td>
              <td>Ukraine</td>
              <td>Russia</td>
            </tr>
            <tr valign="top">
              <td>Roseola</td>
              <td>Vietnam</td>
              <td>Taiwan</td>
              <td>Japan</td>
              <td>Czechia</td>
              <td>Hong Kong</td>
            </tr>
            <tr valign="top">
              <td>Rubella</td>
              <td>Cameroon</td>
              <td>Benin</td>
              <td>Algeria</td>
              <td>Ivory Coast</td>
              <td>Congo-Brazzaville</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="table2fn1">
            <p><sup>a</sup>HFMD: hand, foot, and mouth disease.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>Although some childhood viral diseases such as measles, rubella, or varicella are notifiable diseases [<xref ref-type="bibr" rid="ref28">28</xref>], others such as warts, molluscum contagiosum, roseola, HFMD, or <italic>Pityriasis rosea</italic> are not reportable conditions in most countries, so studies on their changing trends and geographic distribution remain scarce.</p>
      <p>Google Trends, a web-based tracking system of internet search volumes, has been extensively used in the field of infectious diseases, both for monitoring and surveillance purposes [<xref ref-type="bibr" rid="ref6">6</xref>-<xref ref-type="bibr" rid="ref13">13</xref>,<xref ref-type="bibr" rid="ref29">29</xref>], and has been shown to be truly reliable for the prediction of epidemic outbreaks [<xref ref-type="bibr" rid="ref9">9</xref>-<xref ref-type="bibr" rid="ref12">12</xref>].</p>
      <p>Previous data indicate a significant correlation between the volume of search keywords for rubella and measles with monthly reported rubella and measles cases from the Centers for Disease Control and Prevention as well as from the European Center of Disease and Prevention. [<xref ref-type="bibr" rid="ref30">30</xref>]. Our findings indicate increasing interest among the general public regarding measles and, to a lesser extent, rubella, supporting several traditional epidemiological studies assessing a substantial global resurgence of measles cases [<xref ref-type="bibr" rid="ref31">31</xref>-<xref ref-type="bibr" rid="ref33">33</xref>]. The overall outbreak risk for rubella is thought to remain low [<xref ref-type="bibr" rid="ref31">31</xref>]. The decline in vaccination rates, driven by vaccine hesitancy and the lack of confidence in vaccines, has led to recent outbreaks of vaccine-preventable diseases and threatens the public health gains made against these infectious diseases over past decades [<xref ref-type="bibr" rid="ref34">34</xref>,<xref ref-type="bibr" rid="ref35">35</xref>]. These outbreaks are possibly further propagated by travel and migration [<xref ref-type="bibr" rid="ref33">33</xref>]. Infodemiology data suggest that measles may be of particular concern for some African countries (Niger, Chad, Congo-Kinshasa, and Madagascar), supporting Centers for Disease Control and Prevention notices reporting that some parts of Africa are reporting outbreaks of measles [<xref ref-type="bibr" rid="ref36">36</xref>]. Ongoing political instability, conflict, lack of education, and poverty may also serve as major barriers to the success of vaccination programs.</p>
      <p>Varicella still represents the most widespread vaccine-preventable childhood infectious disease in industrialized countries. Due to its relevant burden on health care resources, several countries have introduced varicella vaccination into the recommended routine childhood national immunization schedule. To date, there has been evidence showing a substantial decline in the varicella incidence from some countries that have introduced varicella vaccination [<xref ref-type="bibr" rid="ref37">37</xref>-<xref ref-type="bibr" rid="ref41">41</xref>], but most countries have no data about the impact of vaccination. Unexpectedly, some populations (ie, Republic of Korea) that have implemented universal varicella vaccination are facing increases in the incidence of the disease, possibly explained by primary or secondary vaccine failure [<xref ref-type="bibr" rid="ref42">42</xref>]. Despite the existence of the varicella vaccine, many resource-rich countries have not implemented routine childhood varicella vaccination into their national schedules [<xref ref-type="bibr" rid="ref42">42</xref>] partly because of concerns about whether herpes zoster will increase due to a lack of exogenous boosting. Our data show a worldwide increased internet interest for varicella. This finding is consistent with epidemiological studies showing that varicella incidence rates, while unreliable in the absence of mandatory reporting, tend to increase, possibly due to greater urbanization and population density [<xref ref-type="bibr" rid="ref43">43</xref>].</p>
      <p>Our data also support the resurgence of HFMD, more specifically in East Asia. Since 1998, HFMD has emerged, becoming a major public health concern across the Asia-Pacific region. Although the disease is responsible for over 2 million hospitalizations in Asia annually, sporadic outbreaks have occurred in Europe and in the United States in recent years [<xref ref-type="bibr" rid="ref44">44</xref>].</p>
      <p>The reason(s) why genital herpes decreased during this period is unclear but is in line with epidemiological studies showing that herpes simplex virus type 1 and 2 seroprevalences have had a strong declining trend for at least 2 decades, in both sexes and in all different ethnicities, possibly reflecting improvements in hygiene and living conditions [<xref ref-type="bibr" rid="ref45">45</xref>].</p>
      <p>We found nearly no change (slopes) in interest for molluscum contagiosum. The interest for <italic>Pityriasis rosea</italic> decreased over the study period. Although <italic>Pityriasis rosea</italic> is not uncommon, information regarding its global epidemiology is limited. Our findings may support some data assessing that the incidence of <italic>Pityriasis rosea</italic> may be decreasing [<xref ref-type="bibr" rid="ref46">46</xref>].</p>
      <p>Seasonality is a long-recognized attribute of many viral infections, but the mechanisms underlying seasonality, particularly for person-to-person communicable diseases, remain poorly understood. Seasonality may reflect oscillatory changes in infectiousness, contact patterns, pathogen survival, or host susceptibility. Google Trends has been shown to be suitable for studying seasonal patterns of various skin problems including infectious diseases or conditions such as hair loss [<xref ref-type="bibr" rid="ref47">47</xref>-<xref ref-type="bibr" rid="ref52">52</xref>], but few studies have used eHealth tools to assess the seasonal variations of a cutaneous viral infection.</p>
      <p>Clear seasonality could be observed for some infections. HFMD, varicella, measles, molluscum contagiosum, and warts displayed the highest seasonality coefficients. Peaks of interest were noted in July for HFMD, which is in line with traditional epidemiologic studies showing an association between high temperatures and HFMD [<xref ref-type="bibr" rid="ref53">53</xref>]. The possible seasonality of erythema infectiosum has been poorly investigated. Confirming classic epidemiological studies, the analysis of big data indicate that varicella also has a distinct seasonal pattern [<xref ref-type="bibr" rid="ref54">54</xref>]. However, although classic epidemiologic studies suggest that the highest incidence of varicella [<xref ref-type="bibr" rid="ref55">55</xref>] occurs in winter and spring, internet searches show a peak of interest somewhat later, between April and May. Confirming previous infodemiologic data, we found that the worldwide molluscum contagiosum and wart series showed clear seasonality, with a consistent 12-month oscillation period [<xref ref-type="bibr" rid="ref56">56</xref>]. These results about seasonal patterns should be interpreted with caution, since we analyzed the worldwide interest in cutaneous viral infections including the Southern and Northern Hemispheres. This bias is probably minimized, since 90% of the world’s population and most of the internet users live in the Northern Hemisphere [<xref ref-type="bibr" rid="ref22">22</xref>,<xref ref-type="bibr" rid="ref23">23</xref>]. Viral skin diseases’ seasonality might arise independently of disease incidence, and behavioral trends in skin exposure and self-interest could influence knowledge-seeking for abnormalities such as warts [<xref ref-type="bibr" rid="ref56">56</xref>].</p>
      <p>The main strengths of this study encompass the basic definition of big data, including the “3 V’s”: volume (data sets with large and ever increasing number of observations), variety (the linkage of many structured and unstructured data into a single data set), and velocity (real-time or frequent data updates that are fully automated) [<xref ref-type="bibr" rid="ref4">4</xref>,<xref ref-type="bibr" rid="ref13">13</xref>]. Google Trends supports transparency and credibility because these data are openly available and are not limited by complications related to privacy [<xref ref-type="bibr" rid="ref57">57</xref>], making the analyses replicable by any other investigators. Further, Google Trends topic queries encompass broad literature search terms, search volume data access has remained continuously available since 2008 [<xref ref-type="bibr" rid="ref58">58</xref>], and the search is not restricted by language.</p>
      <p>There are some limitations associated with this analysis. Google Trends provides only an RSV index, not the absolute search volume, and does not provide a way to calculate the search volume index. Google Trends also only provides data related to the selected search terms. Although we chose search terms as inclusively as possible, people looking for information on Google may have chosen other terms. The motivation of Google users is not known. As a corollary, the data obtained from Google Trends cannot be independently verified. The spike of internet searches may be attributed to various factors. It may be due to changes in case numbers in the community and changes driven by government agencies’ announcements, educational purposes, or media coverage (newspapers and newscasts), influencing the web-based research of the population and leading to concerns about the increased risk of obtaining false-positive results [<xref ref-type="bibr" rid="ref59">59</xref>,<xref ref-type="bibr" rid="ref60">60</xref>]. Another limitation is that the participant sample was biased toward a certain segment of the population—those with internet access and using Google Search instead of other search engines. However, this bias is mitigated by the fact that as of March 2015, Google accounted for an estimated 65% of all internet search traffic, whereas the next most popular search engine accounted for only 20% of traffic during a given month [<xref ref-type="bibr" rid="ref61">61</xref>]. Although it is common among the whole population to make web-based health-related searches, younger people tend to use the internet more often. There is also a lack of detailed information on the algorithms Google Trends uses to analyze this search data. For instance, RSV values show a high dependence on the day they are gathered, which can invalidate the reliability of a data set [<xref ref-type="bibr" rid="ref57">57</xref>]. The collection of worldwide RSVs might minimize these oscillations [<xref ref-type="bibr" rid="ref57">57</xref>]. It remains also possible that the large amount of data does not necessarily eliminate sources of systematic error and may even amplify them. Finally, Google Trends changed the geographic assignment for internet searches on Jan 1, 2011, and data collection in 2016, which was reflected by Google Trends displaying a respective note in the displayed graphs, but no further information was given [<xref ref-type="bibr" rid="ref58">58</xref>].</p>
      <p>In conclusion, this is the first study using an open web-based infoveillance tool, suggesting that although the incidence of non–vaccine-preventable skin infections is not changing or may be declining, the incidence of vaccinable diseases such as measles, rubella, and varicella is increasing worldwide. The surprising reemergence of measles and other diseases can be attributed to the rise of the anti-vaccination movement, in which groups of people refuse to be vaccinated or have their children vaccinated either out of fear, misinformation, or personal beliefs. The huge potential of the approach of analyzing Google search data could be used in the immediate future to generate timely alerts for clinical epidemiologists on disease outbreaks much earlier than conventional health epidemiology.</p>
    </sec>
  </body>
  <back>
    <app-group>
      <supplementary-material id="app1">
        <label>Multimedia Appendix 1</label>
        <p>Technical details concerning the statistical model and analysis.</p>
        <media xlink:href="derma_v5i4e35034_app1.doc" xlink:title="DOC File , 49 KB"/>
      </supplementary-material>
    </app-group>
    <glossary>
      <title>Abbreviations</title>
      <def-list>
        <def-item>
          <term id="abb1">HFMD</term>
          <def>
            <p>hand, foot, and mouth disease</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb2">RSV</term>
          <def>
            <p>relative search volume</p>
          </def>
        </def-item>
      </def-list>
    </glossary>
    <fn-group>
      <fn fn-type="conflict">
        <p>None declared.</p>
      </fn>
    </fn-group>
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