Global prevalence and distribution of coinfection of malaria, dengue and chikungunya: a systematic review
Identifieur interne : 000120 ( Pmc/Corpus ); précédent : 000119; suivant : 000121Global prevalence and distribution of coinfection of malaria, dengue and chikungunya: a systematic review
Auteurs : Nasir Salam ; Shoeb Mustafa ; Abdul Hafiz ; Anis Ahmad Chaudhary ; Farah Deeba ; Shama ParveenSource :
- BMC Public Health [ 1471-2458 ] ; 2018.
Abstract
Malaria, Dengue and Chikungunya are vector borne diseases with shared endemic profiles and symptoms. Coinfections with any of these diseases could have fatal outcomes if left undiagnosed. Understanding the prevalence and distribution of coinfections is necessary to improve diagnosis and designing therapeutic interventions.
We have carried out a systematic search of the published literature based on PRISMA guidelines to identify cases of Malaria, Dengue and Chikungunya coinfections. We systematically reviewed the literature to identify eligible studies and extracted data regarding cases of coinfection from cross sectional studies, case reports, retrospective studies, prospective observational studies and surveillance reports.
Care full screening resulted in 104 publications that met the eligibility criteria and reported Malaria/Dengue, Dengue/Chikungunya, Malaria/Chikungunya and Malaria/Dengue/Chikungunya coinfections. These coinfections were spread over six geographical locations and 42 different countries and are reported more frequently in the last 15 years possibly due to expanding epidemiology of Dengue and Chikungunya. Few of these reports have also analysed distinguishing features of coinfections. Malaria/Dengue coinfections were the most common coinfection followed by Dengue/Chikungunya, Malaria/Chikungunya and Malaria/Dengue/Chikungunya coinfections.
We have comprehensively reviewed the literature associated with cases of coinfections of three important vector borne diseases to present a clear picture of their prevalence and distribution across the globe. The frequency of coinfections presented in the study suggests proper diagnosis, surveillance and management of cases of coinfection to avoid poor prognosis of the underlying etiology.
The online version of this article (10.1186/s12889-018-5626-z) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s12889-018-5626-z
PubMed: 29879935
PubMed Central: 5992662
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PMC:5992662Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Global prevalence and distribution of coinfection of malaria, dengue and chikungunya: a systematic review</title><author><name sortKey="Salam, Nasir" sort="Salam, Nasir" uniqKey="Salam N" first="Nasir" last="Salam">Nasir Salam</name><affiliation><nlm:aff id="Aff1">College of Medicine, Al-Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia</nlm:aff></affiliation></author><author><name sortKey="Mustafa, Shoeb" sort="Mustafa, Shoeb" uniqKey="Mustafa S" first="Shoeb" last="Mustafa">Shoeb Mustafa</name><affiliation><nlm:aff id="Aff1">College of Medicine, Al-Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia</nlm:aff></affiliation></author><author><name sortKey="Hafiz, Abdul" sort="Hafiz, Abdul" uniqKey="Hafiz A" first="Abdul" last="Hafiz">Abdul Hafiz</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9137 6644</institution-id><institution-id institution-id-type="GRID">grid.412832.e</institution-id><institution>Department of Parasitology,</institution><institution>College of Medicine, Umm Al-Qura University,</institution></institution-wrap>Mecca, Saudi Arabia</nlm:aff></affiliation></author><author><name sortKey="Chaudhary, Anis Ahmad" sort="Chaudhary, Anis Ahmad" uniqKey="Chaudhary A" first="Anis Ahmad" last="Chaudhary">Anis Ahmad Chaudhary</name><affiliation><nlm:aff id="Aff1">College of Medicine, Al-Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia</nlm:aff></affiliation></author><author><name sortKey="Deeba, Farah" sort="Deeba, Farah" uniqKey="Deeba F" first="Farah" last="Deeba">Farah Deeba</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0498 8255</institution-id><institution-id institution-id-type="GRID">grid.411818.5</institution-id><institution>Centre for Interdisciplinary Research in Basic Sciences,</institution><institution>Jamia Millia Islamia,</institution></institution-wrap>New Delhi, 110025 India</nlm:aff></affiliation></author><author><name sortKey="Parveen, Shama" sort="Parveen, Shama" uniqKey="Parveen S" first="Shama" last="Parveen">Shama Parveen</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0498 8255</institution-id><institution-id institution-id-type="GRID">grid.411818.5</institution-id><institution>Centre for Interdisciplinary Research in Basic Sciences,</institution><institution>Jamia Millia Islamia,</institution></institution-wrap>New Delhi, 110025 India</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">29879935</idno><idno type="pmc">5992662</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992662</idno><idno type="RBID">PMC:5992662</idno><idno type="doi">10.1186/s12889-018-5626-z</idno><date when="2018">2018</date><idno type="wicri:Area/Pmc/Corpus">000120</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000120</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Global prevalence and distribution of coinfection of malaria, dengue and chikungunya: a systematic review</title><author><name sortKey="Salam, Nasir" sort="Salam, Nasir" uniqKey="Salam N" first="Nasir" last="Salam">Nasir Salam</name><affiliation><nlm:aff id="Aff1">College of Medicine, Al-Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia</nlm:aff></affiliation></author><author><name sortKey="Mustafa, Shoeb" sort="Mustafa, Shoeb" uniqKey="Mustafa S" first="Shoeb" last="Mustafa">Shoeb Mustafa</name><affiliation><nlm:aff id="Aff1">College of Medicine, Al-Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia</nlm:aff></affiliation></author><author><name sortKey="Hafiz, Abdul" sort="Hafiz, Abdul" uniqKey="Hafiz A" first="Abdul" last="Hafiz">Abdul Hafiz</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9137 6644</institution-id><institution-id institution-id-type="GRID">grid.412832.e</institution-id><institution>Department of Parasitology,</institution><institution>College of Medicine, Umm Al-Qura University,</institution></institution-wrap>Mecca, Saudi Arabia</nlm:aff></affiliation></author><author><name sortKey="Chaudhary, Anis Ahmad" sort="Chaudhary, Anis Ahmad" uniqKey="Chaudhary A" first="Anis Ahmad" last="Chaudhary">Anis Ahmad Chaudhary</name><affiliation><nlm:aff id="Aff1">College of Medicine, Al-Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia</nlm:aff></affiliation></author><author><name sortKey="Deeba, Farah" sort="Deeba, Farah" uniqKey="Deeba F" first="Farah" last="Deeba">Farah Deeba</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0498 8255</institution-id><institution-id institution-id-type="GRID">grid.411818.5</institution-id><institution>Centre for Interdisciplinary Research in Basic Sciences,</institution><institution>Jamia Millia Islamia,</institution></institution-wrap>New Delhi, 110025 India</nlm:aff></affiliation></author><author><name sortKey="Parveen, Shama" sort="Parveen, Shama" uniqKey="Parveen S" first="Shama" last="Parveen">Shama Parveen</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0498 8255</institution-id><institution-id institution-id-type="GRID">grid.411818.5</institution-id><institution>Centre for Interdisciplinary Research in Basic Sciences,</institution><institution>Jamia Millia Islamia,</institution></institution-wrap>New Delhi, 110025 India</nlm:aff></affiliation></author></analytic><series><title level="j">BMC Public Health</title><idno type="eISSN">1471-2458</idno><imprint><date when="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p id="Par1">Malaria, Dengue and Chikungunya are vector borne diseases with shared endemic profiles and symptoms. Coinfections with any of these diseases could have fatal outcomes if left undiagnosed. Understanding the prevalence and distribution of coinfections is necessary to improve diagnosis and designing therapeutic interventions.</p></sec><sec><title>Methods</title><p id="Par2">We have carried out a systematic search of the published literature based on PRISMA guidelines to identify cases of Malaria, Dengue and Chikungunya coinfections. We systematically reviewed the literature to identify eligible studies and extracted data regarding cases of coinfection from cross sectional studies, case reports, retrospective studies, prospective observational studies and surveillance reports.</p></sec><sec><title>Results</title><p id="Par3">Care full screening resulted in 104 publications that met the eligibility criteria and reported Malaria/Dengue, Dengue/Chikungunya, Malaria/Chikungunya and Malaria/Dengue/Chikungunya coinfections. These coinfections were spread over six geographical locations and 42 different countries and are reported more frequently in the last 15 years possibly due to expanding epidemiology of Dengue and Chikungunya. Few of these reports have also analysed distinguishing features of coinfections. Malaria/Dengue coinfections were the most common coinfection followed by Dengue/Chikungunya, Malaria/Chikungunya and Malaria/Dengue/Chikungunya coinfections. <italic>P. falciparum</italic> and <italic>P. vivax</italic> were the commonest species found in cases of malaria coinfections and Dengue serotype-4 commonest serotype in cases of dengue coinfections. Most studies were reported from India. Nigeria and India were the only two countries from where all possible combinations of coinfections were reported.</p></sec><sec><title>Conclusion</title><p id="Par4">We have comprehensively reviewed the literature associated with cases of coinfections of three important vector borne diseases to present a clear picture of their prevalence and distribution across the globe. The frequency of coinfections presented in the study suggests proper diagnosis, surveillance and management of cases of coinfection to avoid poor prognosis of the underlying etiology.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (10.1186/s12889-018-5626-z) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Kilpatrick, Am" uniqKey="Kilpatrick A">AM Kilpatrick</name></author><author><name sortKey="Randolph, Se" uniqKey="Randolph S">SE Randolph</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bhatt, S" uniqKey="Bhatt S">S Bhatt</name></author><author><name sortKey="Gething, Pw" uniqKey="Gething P">PW Gething</name></author><author><name sortKey="Brady, Oj" uniqKey="Brady O">OJ Brady</name></author><author><name sortKey="Messina, Jp" uniqKey="Messina J">JP 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<front><journal-meta><journal-id journal-id-type="nlm-ta">BMC Public Health</journal-id><journal-id journal-id-type="iso-abbrev">BMC Public Health</journal-id><journal-title-group><journal-title>BMC Public Health</journal-title></journal-title-group><issn pub-type="epub">1471-2458</issn><publisher><publisher-name>BioMed Central</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">29879935</article-id><article-id pub-id-type="pmc">5992662</article-id><article-id pub-id-type="publisher-id">5626</article-id><article-id pub-id-type="doi">10.1186/s12889-018-5626-z</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Global prevalence and distribution of coinfection of malaria, dengue and chikungunya: a systematic review</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0001-9133-1304</contrib-id><name><surname>Salam</surname><given-names>Nasir</given-names></name><address><email>nsalam@imamu.edu.sa</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Mustafa</surname><given-names>Shoeb</given-names></name><address><email>drshoebmustafa@gmail.com</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Hafiz</surname><given-names>Abdul</given-names></name><address><email>aaahafiz@uqu.edu.sa</email></address><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Chaudhary</surname><given-names>Anis Ahmad</given-names></name><address><email>anis.chaudhary@gmail.com</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Deeba</surname><given-names>Farah</given-names></name><address><email>farahdeeba19@gmail.com</email></address><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Parveen</surname><given-names>Shama</given-names></name><address><email>shamp25@yahoo.com</email></address><xref ref-type="aff" rid="Aff3">3</xref></contrib><aff id="Aff1"><label>1</label>College of Medicine, Al-Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia</aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9137 6644</institution-id><institution-id institution-id-type="GRID">grid.412832.e</institution-id><institution>Department of Parasitology,</institution><institution>College of Medicine, Umm Al-Qura University,</institution></institution-wrap>Mecca, Saudi Arabia</aff><aff id="Aff3"><label>3</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0498 8255</institution-id><institution-id institution-id-type="GRID">grid.411818.5</institution-id><institution>Centre for Interdisciplinary Research in Basic Sciences,</institution><institution>Jamia Millia Islamia,</institution></institution-wrap>New Delhi, 110025 India</aff></contrib-group><pub-date pub-type="epub"><day>8</day><month>6</month><year>2018</year></pub-date><pub-date pub-type="pmc-release"><day>8</day><month>6</month><year>2018</year></pub-date><pub-date pub-type="collection"><year>2018</year></pub-date><volume>18</volume><elocation-id>710</elocation-id><history><date date-type="received"><day>19</day><month>2</month><year>2018</year></date><date date-type="accepted"><day>29</day><month>5</month><year>2018</year></date></history><permissions><copyright-statement>© The Author(s). 2018</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold>This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>) applies to the data made available in this article, unless otherwise stated.</license-p></license></permissions><abstract id="Abs1"><sec><title>Background</title><p id="Par1">Malaria, Dengue and Chikungunya are vector borne diseases with shared endemic profiles and symptoms. Coinfections with any of these diseases could have fatal outcomes if left undiagnosed. Understanding the prevalence and distribution of coinfections is necessary to improve diagnosis and designing therapeutic interventions.</p></sec><sec><title>Methods</title><p id="Par2">We have carried out a systematic search of the published literature based on PRISMA guidelines to identify cases of Malaria, Dengue and Chikungunya coinfections. We systematically reviewed the literature to identify eligible studies and extracted data regarding cases of coinfection from cross sectional studies, case reports, retrospective studies, prospective observational studies and surveillance reports.</p></sec><sec><title>Results</title><p id="Par3">Care full screening resulted in 104 publications that met the eligibility criteria and reported Malaria/Dengue, Dengue/Chikungunya, Malaria/Chikungunya and Malaria/Dengue/Chikungunya coinfections. These coinfections were spread over six geographical locations and 42 different countries and are reported more frequently in the last 15 years possibly due to expanding epidemiology of Dengue and Chikungunya. Few of these reports have also analysed distinguishing features of coinfections. Malaria/Dengue coinfections were the most common coinfection followed by Dengue/Chikungunya, Malaria/Chikungunya and Malaria/Dengue/Chikungunya coinfections. <italic>P. falciparum</italic> and <italic>P. vivax</italic> were the commonest species found in cases of malaria coinfections and Dengue serotype-4 commonest serotype in cases of dengue coinfections. Most studies were reported from India. Nigeria and India were the only two countries from where all possible combinations of coinfections were reported.</p></sec><sec><title>Conclusion</title><p id="Par4">We have comprehensively reviewed the literature associated with cases of coinfections of three important vector borne diseases to present a clear picture of their prevalence and distribution across the globe. The frequency of coinfections presented in the study suggests proper diagnosis, surveillance and management of cases of coinfection to avoid poor prognosis of the underlying etiology.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (10.1186/s12889-018-5626-z) contains supplementary material, which is available to authorized users.</p></sec></abstract><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2018</meta-value></custom-meta></custom-meta-group></article-meta></front><body><sec id="Sec1"><title>Background</title><p id="Par11">In recent years the spread of vector borne diseases has gained concern worldwide, especially in tropical and subtropical regions because of their recurring outbreaks [<xref ref-type="bibr" rid="CR1">1</xref>]. Some of these diseases have become endemic in many areas causing millions of cases every year [<xref ref-type="bibr" rid="CR2">2</xref>]. The most common of these diseases includes Malaria, Dengue and Chikungunya spread by mosquito bites. Malaria has been long recognized as a significant public health threat with around 212 million cases reported in 2015 alone [<xref ref-type="bibr" rid="CR3">3</xref>]. Malaria is caused by five different species of Protozoal parasite, <italic>Plasmodium</italic>. These include <italic>P. falciparum, P. ovale, P. malariae, P. vivax and P. knowlesi</italic> that are carried and spread by <italic>Anopheles</italic> mosquito [<xref ref-type="bibr" rid="CR4">4</xref>, <xref ref-type="bibr" rid="CR5">5</xref>]. Dengue and Chikungunya are caused by viruses named Dengue virus (DENV) and Chikungunya virus (CHIKV) respectively. Both are spread by common mosquito vectors <italic>Aedes s p.</italic> Dengue viruses have four serotypes DENV-1, 2,3 and 4 [<xref ref-type="bibr" rid="CR6">6</xref>]. As many as 400 million people are affected with Dengue every year [<xref ref-type="bibr" rid="CR7">7</xref>]. Chikungunya follows somewhat unique pattern of spread across the world, it has the potential to emerge and re-emerge, drastically affecting a population and then remaining undetected for years [<xref ref-type="bibr" rid="CR8">8</xref>]. In recent years many tropical countries have seen an unexpected rise and spread in cases of Dengue and Chikungunya [<xref ref-type="bibr" rid="CR9">9</xref>].</p><p id="Par12">These three vector borne diseases share an overlapping epidemic pattern with most cases reported from tropical regions of the world. Several studies have been published reporting co-circulation of Malaria, Dengue and Chikungunya [<xref ref-type="bibr" rid="CR10">10</xref>, <xref ref-type="bibr" rid="CR11">11</xref>]. Apart from shared endemicity, the three diseases also share similar clinical presentation with febrility as the most common symptom. There are several distinguishing features also, like periodic increase and decrease of fever in Malaria, hemorrhagic conditions and depletion of platelet count in Dengue and severe arthralgia in case of Chikungunya infection [<xref ref-type="bibr" rid="CR12">12</xref>, <xref ref-type="bibr" rid="CR13">13</xref>]. The cumulative burden of these infections has increased in recent times with frequent outbreak of Dengue and Chikungunya being reported from several parts of the world. Global travel and rapid urbanisation are important factors that have contributed in expansion of disease endemicity by introducing the vector population to exotic surroundings [<xref ref-type="bibr" rid="CR14">14</xref>].</p><p id="Par13">Simultaneous infections with more than one infectious agent complicate the diagnosis and course of treatment available. Due to the similar nature of initial symptoms for Malaria, Dengue and Chikungunya and overlapping endemicity, misdiagnosis of dual infection as monoinfection is a real possibility. Indeed several reports have been published reporting such scenarios. These arthropod borne diseases affect some of the poorest countries and in resource poor settings; clinician might rely on symptoms and endemicity for diagnosis, which might lead to underdiagnosis of cocirculating pathogens [<xref ref-type="bibr" rid="CR15">15</xref>]. Despite similar clinical presentation the course of treatment is entirely different for all three diseases. Malaria is treated using antimalarial drugs. In case of Dengue and Chikungunya no vaccine or drug is available and clinicians rely on supportive therapy [<xref ref-type="bibr" rid="CR13">13</xref>, <xref ref-type="bibr" rid="CR16">16</xref>]. Any delay in either diagnosis or start of therapy for any of these infections could have fatal outcomes. Also, there is lack of sufficient information on how concurrent infections affect disease severity and outcome. Several studies have been published that report cases of concurrent infection with two of these pathogens and in rare instances concurrent infection with all three vector borne infections. Such reports have the potential to inform public health officials and clinicians about the prevalence, disease severity and treatment options available for concurrent infections. The purpose of the present review is to assess the prevalence of such infections by thorough search and analysis of published literature.</p></sec><sec id="Sec2"><title>Methodology</title><sec id="Sec3"><title>Search strategy</title><p id="Par14">We did a review based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to identify all relevant publications pertaining to the prevalence of Malaria, Dengue and Chikungunya coinfection. We systematically searched PubMed and Web of Knowledge from inception up to April 2018, using the following search terms anywhere in the articles: Malaria AND Dengue or Malaria AND Chikungunya or Dengue AND Chikungunya. We searched without any bar on language, publication or nature of studies. To identify additional studies, reference list of publications were carefully screened.</p><sec id="Sec4"><title>Eligibility criteria</title><p id="Par15">Initial assessment was based on review of title and abstract of all studies. Full texts of potentially relevant studies were further analysed for coinfection prevalence data. Cross-sectional studies, retrospective analysis and case reports with full text availability and reporting data about any/all of the coinfections were included in the study. We excluded studies carried out in animals, reviews, letters, opinion pieces, grey literature, dissertations and conference abstracts.</p></sec><sec id="Sec5"><title>Data extraction</title><p id="Par16">The data extracted from the selected publications included first author, date of survey, place where the study was carried out, sample size and age, type of diagnostic testing performed, study design and prevalence of coinfection. All the data was entered in an excel file and double-checked.</p></sec></sec><sec id="Sec6"><title>Prevalence mapping</title><p id="Par17">The extracted data was used to create a map of prevalence of coinfection cases. All the cases reported were from seven geographical locations, South Asia, Africa, Southeast Asia, South America, North America, Caribbean and the Middle East. A total of 19 countries reported cases of Malaria/Dengue coinfection; while 24 countries reported coinfection cases of Dengue/Chikungunya. Malaria/Chikungunya cases were reported from 6 countries. Malaria/Dengue/Chikungunya coinfections were reported from only 3 countries. The maps were created using openly available maps (<ext-link ext-link-type="uri" xlink:href="https://www.freeworldmaps.net">https://www.freeworldmaps.net</ext-link>).</p></sec></sec><sec id="Sec7"><title>Results</title><p id="Par18">We were able to identify 109 publications that reported the data for any coinfections (Fig. <xref rid="Fig1" ref-type="fig">1</xref>, Additional file <xref rid="MOESM1" ref-type="media">1</xref>: Table S1). The full text of 104 publications were available out of which 48 were cross sectional studies, 37 were case reports, 13 were retrospective analysis, 5 were prospective studies and 1 surveillance report [<xref ref-type="bibr" rid="CR17">17</xref>–<xref ref-type="bibr" rid="CR120">120</xref>]. 49 studies reported only Malaria/Dengue coinfections (Table <xref rid="Tab1" ref-type="table">1</xref>) while 44 studies reported only Dengue/Chikungunya coinfections (Table <xref rid="Tab2" ref-type="table">2</xref>). 1 study reported only Malaria/Chikungunya infection. 3 studies reported both Malaria/Dengue and Malaria/Chikungunya coinfections (Table <xref rid="Tab3" ref-type="table">3</xref>) and 1 study reported Malaria/Dengue, Dengue/Chikungunya and Malaria/Chikungunya coinfections. Malaria/Dengue/Chikungunya coinfections were reported by 4 separate studies (Table <xref rid="Tab4" ref-type="table">4</xref>). 2 studies reported Malaria/Dengue, Dengue/Chikungunya, Malaria/Chikungunya and Malaria/Dengue/Chikungunya coinfections. All of the studies, except two, were published after year 2005. Cases of coinfections were reported from all age groups and two studies from India and Burma reported data from only pregnant females. Blood smear was the most prevalent method for detection of Malaria parasite, while NS1 (Non-structural protein-1) and immunoglobulin ELISA were the most common methods for the detection of Dengue. IgM ELISA was the predominant method for the detection of most cases of Chikungunya. In 14 studies <italic>P. falciparum</italic> was the cause of Malaria while another 13 reported <italic>P. vivax</italic> as the infecting species alongside coinfecting arbovirus. 12 studies reported both <italic>P. falciparum</italic> and <italic>P. vivax</italic> with Dengue virus in the same population. Another 5 studies reported <italic>P. falciparum</italic>, <italic>P. vivax</italic> and Dengue virus in the same individuals. <italic>P. knowlesi</italic> was reported by two studies and <italic>P. ovale</italic> was reported by one study.<fig id="Fig1"><label>Fig. 1</label><caption><p>Schematic representation of the study selection process</p></caption><graphic xlink:href="12889_2018_5626_Fig1_HTML" id="MO1"></graphic></fig><table-wrap id="Tab1"><label>Table 1</label><caption><p>Coinfection cases of Malaria and Dengue</p></caption><table frame="hsides" rules="groups"><thead><tr><th>S.No.</th><th>Citation</th><th>Place</th><th>Year</th><th>Study design</th><th>N</th><th>Positive for coinfection</th><th>Coinfection (%)</th><th>Age</th><th>Diagnostic test ML/DN</th><th>Remarks</th></tr></thead><tbody><tr><td colspan="11">South Asia</td></tr><tr><td>1</td><td>Abbasi [<xref ref-type="bibr" rid="CR17">17</xref>]</td><td>Karachi,<break></break>Pakistan</td><td>Sept.2007-Jan. 2008</td><td>Cross sectional</td><td>112</td><td>26</td><td>23</td><td>13–70</td><td>Blood smear / IgM and IgG ELISA</td><td><italic>P. vivax- 25, P. falciparum</italic>- 1</td></tr><tr><td>2</td><td>Ahmad [<xref ref-type="bibr" rid="CR18">18</xref>]</td><td>Uttarakhand, India</td><td>Dec 2012-Dec2013</td><td>Retrospective observational studies</td><td>233</td><td>9</td><td>3.8</td><td>38.6 ± 16</td><td>Blood smear/ IgM ELISA</td><td>NM</td></tr><tr><td>3</td><td>Alam [<xref ref-type="bibr" rid="CR19">19</xref>]</td><td>Patna,<break></break>India</td><td>2013</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>42</td><td>Blood smear /NS1, IgM and IgG ELISA</td><td><italic>P. falciparum</italic></td></tr><tr><td>4</td><td>Ali [<xref ref-type="bibr" rid="CR20">20</xref>]</td><td>Rawalpindi,<break></break>Pakistan</td><td>Nov. 2003-Oct. 2004</td><td>Cross sectional</td><td>800</td><td>9</td><td>1</td><td>17–50 years</td><td>Blood smear /IgM ELISA</td><td><italic>P. vivax-8, P. falciparum-1</italic></td></tr><tr><td>5</td><td>Arya [<xref ref-type="bibr" rid="CR21">21</xref>]</td><td>Delhi,<break></break>India</td><td>2003</td><td>Case report</td><td>2</td><td>2</td><td>NA</td><td>35 and 63 years</td><td>Blood smear /IgM ELISA</td><td><italic>P. vivax</italic></td></tr><tr><td>6</td><td>Assir [<xref ref-type="bibr" rid="CR22">22</xref>]</td><td>Lahore,<break></break>Pakistan</td><td>Aug- Nov 2012</td><td>Cross sectional</td><td>856</td><td>17</td><td>2</td><td>12–32</td><td>Blood smear /PCR, NS1 and IgM ELISA</td><td><italic>P. vivax</italic> - 14, <italic>P. falciparum</italic>-3</td></tr><tr><td>7</td><td>Barua [<xref ref-type="bibr" rid="CR23">23</xref>]</td><td>Mumbai,<break></break>India</td><td>June-Nov. 2014, June -Nov. 2015</td><td>Retrospective analysis</td><td>573</td><td>44</td><td>8</td><td>NM</td><td>Blood smear / NS1 and IgM ELISA</td><td>NM</td></tr><tr><td>8</td><td>Bhagat [<xref ref-type="bibr" rid="CR24">24</xref>]</td><td>Mumbai,<break></break>India</td><td>2014</td><td>Case report</td><td>3</td><td>3</td><td>NA</td><td>8 months −12 year</td><td>Blood smear, RDT/NS1, IgM and IgG ELISA</td><td><italic>P. vivax</italic></td></tr><tr><td>9</td><td>Bhalla [<xref ref-type="bibr" rid="CR25">25</xref>]</td><td>Delhi,<break></break>India</td><td>2006</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>21</td><td>Blood smear /IgM ELISA</td><td><italic>P. falciparum</italic></td></tr><tr><td>10</td><td>Chander [<xref ref-type="bibr" rid="CR26">26</xref>]</td><td>Chandigarh,<break></break>India</td><td>2009</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>28</td><td>Blood smear /IgM ELISA</td><td><italic>P. falciparum</italic></td></tr><tr><td>11</td><td>Deresinski [<xref ref-type="bibr" rid="CR27">27</xref>]</td><td>USA, infected in India</td><td>2003, Dec</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>27</td><td>Blood smear/IgM and IgG ELISA</td><td><italic>P. vivax</italic></td></tr><tr><td>12</td><td>Faruque [<xref ref-type="bibr" rid="CR28">28</xref>]</td><td>Chittagong,<break></break>Bangladesh</td><td>Dec. 2008-Nov. 2009</td><td>Cross sectional</td><td>720</td><td>1</td><td>0.1</td><td>All ages</td><td>RDT/IgM ELISA</td><td><italic>P. vivax</italic></td></tr><tr><td>13</td><td>Hati [<xref ref-type="bibr" rid="CR29">29</xref>]</td><td>Kolkata,<break></break>India</td><td>Aug 2005-Dec 2010</td><td>Cross sectional</td><td>2971</td><td>46</td><td>1.5</td><td>NM</td><td>Blood smear /IgM and IgG ELISA</td><td><italic>P. vivax</italic>-28, <italic>P. falciparum</italic>-18</td></tr><tr><td>14</td><td>Kaushik [<xref ref-type="bibr" rid="CR30">30</xref>]</td><td>Dehradun,<break></break>India</td><td>2006</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>26</td><td>Blood smear/ IgM and IgG ELISA</td><td><italic>P. vivax</italic> + <italic>P. falciparum</italic></td></tr><tr><td>15</td><td>Malhotra [<xref ref-type="bibr" rid="CR31">31</xref>]</td><td>Patiala,<break></break>India</td><td>2012</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>27</td><td>Blood smear /NS1 and IgM ELISA</td><td><italic>P. vivax</italic></td></tr><tr><td>16</td><td>Mittal [<xref ref-type="bibr" rid="CR32">32</xref>]</td><td>Dehradun, India</td><td>Dec 2012- Nov 2013</td><td>Retrospective observational study</td><td>2547</td><td>8</td><td>0.3</td><td>Above 18</td><td>Blood film, RDT/IgM, NS1 ELISA</td><td>NM</td></tr><tr><td>17</td><td>Mohapatra [<xref ref-type="bibr" rid="CR33">33</xref>]</td><td>Odisha,<break></break>India</td><td>June-Sep 2011</td><td>Prospective observational study</td><td>469</td><td>27</td><td>6</td><td>NM</td><td>Blood smear /IgM and NS1 ELISA</td><td><italic>P. falciparum</italic>-24, <italic>P. vivax</italic> – 2, <italic>P. falciparum</italic> + <italic>P. vivax</italic> - 1</td></tr><tr><td>18</td><td>Mørch [<xref ref-type="bibr" rid="CR34">34</xref>]</td><td>Assam, Bihar, Chhattisgarh, Maharashtra, Anantpur Tamilnadu<break></break>India</td><td>April 2011–November 2012</td><td>Cross sectional</td><td>1564</td><td>58</td><td>3.7</td><td>34 mean age</td><td>Blood smear/IgM, NS1 ELISA/</td><td>NM</td></tr><tr><td>19</td><td>Mushtaq [<xref ref-type="bibr" rid="CR35">35</xref>]</td><td>Srinagar, infected in Delhi,<break></break>India</td><td>Oct - 2012</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>25</td><td>Blood smear, RDT/ IgM ELISA</td><td><italic>P. falciparum</italic> + <italic>P. vivax</italic></td></tr><tr><td>20</td><td>Pande [<xref ref-type="bibr" rid="CR36">36</xref>]</td><td>Meerut,<break></break>India</td><td>2013</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>25</td><td>Blood smear /NS1 and IgM ELISA</td><td><italic>P. falciparum, P. vivax</italic></td></tr><tr><td>21</td><td>Raja [<xref ref-type="bibr" rid="CR37">37</xref>]</td><td>Chennai,<break></break>India</td><td>May 2013- Jan 2014</td><td>Cross sectional</td><td>100</td><td>3</td><td>3</td><td>NM</td><td>Blood smear/ELISA</td><td>NM</td></tr><tr><td>22</td><td>Rani [<xref ref-type="bibr" rid="CR38">38</xref>]</td><td>Hyderabad, India</td><td>2015</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>30s</td><td>Blood smear/IgM ELISA</td><td>NM</td></tr><tr><td>23</td><td>Rao [<xref ref-type="bibr" rid="CR39">39</xref>]</td><td>Odisha (Angul), India</td><td>Jan-Dec 2013</td><td>Cross sectional</td><td>1980</td><td>22</td><td>1</td><td>All ages</td><td>Blood smear, RDT/ IgM and NS1 ELISA, PCR</td><td><italic>P. falciparum</italic>- 12, <italic>P. vivax-</italic> 10</td></tr><tr><td>24</td><td>Singh [<xref ref-type="bibr" rid="CR40">40</xref>]</td><td>Dehradun, India</td><td>July-Nov 2013</td><td>Retrospective</td><td>1141</td><td>9</td><td>0.8</td><td>12–80</td><td>Blood smear/IgM, NS1 ELISA</td><td>NM</td></tr><tr><td>25</td><td>Saksena [<xref ref-type="bibr" rid="CR41">41</xref>]</td><td>Delhi,<break></break>India</td><td>2017</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>17 male</td><td>RMAT, PCR/IgM ELISA</td><td><italic>P. vivax, P. falciparum</italic></td></tr><tr><td>26</td><td>Singla [<xref ref-type="bibr" rid="CR42">42</xref>]</td><td>Chandigarh, India</td><td>Jan 2011-Dec 2012</td><td>Cross sectional</td><td>300</td><td>1</td><td>0.3</td><td>NM</td><td>NM/NS1 and IgM ELISA</td><td><italic>P. vivax</italic></td></tr><tr><td>27</td><td>Shah [<xref ref-type="bibr" rid="CR43">43</xref>]</td><td>Ahmedabad, India</td><td>June 2013-Nov 2014</td><td>Retrospective</td><td>8364</td><td>27</td><td>0.3</td><td>NM</td><td>Blood smear/NS1, IgM ELISA</td><td><italic>P. vivax</italic> + DENV-17, <italic>P. falciparum</italic> + DENV-9,<break></break>P. <italic>falciparum</italic> + P. <italic>vivax</italic> + DENV-1</td></tr><tr><td>28</td><td>Thangaratham [<xref ref-type="bibr" rid="CR44">44</xref>]</td><td>Alappuzha,<break></break>Kerala</td><td>2006</td><td>Case report</td><td>1</td><td>1</td><td>NM</td><td>22</td><td>Blood smear /IgM ELISA</td><td><italic>P. vivax,</italic> DENV2</td></tr><tr><td>29</td><td>Yasir [<xref ref-type="bibr" rid="CR45">45</xref>]</td><td>Karachi,<break></break>Pakistan</td><td>April 2013-Jan 2014</td><td>Cross sectional</td><td>159</td><td>5</td><td>3</td><td>15–53 years</td><td>Blood smear /IgM ELISA</td><td>NM</td></tr><tr><td colspan="11">Africa</td></tr><tr><td>30</td><td>Ayorinde [<xref ref-type="bibr" rid="CR46">46</xref>]</td><td>Ogun, Nigeria</td><td>April-May 2014</td><td>Cross sectional</td><td>60</td><td>1</td><td>2</td><td>All ages</td><td>Blood smear, RDT, PCR/NS1, IgM and IgG ELISA</td><td><italic>P. falciparum</italic></td></tr><tr><td>31</td><td>Baba [<xref ref-type="bibr" rid="CR47">47</xref>]</td><td>Nigeria</td><td>July-Dec. 2008</td><td>Cross sectional</td><td>310</td><td>18</td><td>6</td><td>All ages</td><td>Blood smear /PRNT</td><td><italic>P. falciparum</italic></td></tr><tr><td>32</td><td>Charrel [<xref ref-type="bibr" rid="CR48">48</xref>]</td><td>France, infected in Guinea, Senegal and Sierra Leone</td><td>2004, march</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>37</td><td>Blood smear /IgM and IgG ELISA</td><td><italic>P. falciparum,</italic> DENV3</td></tr><tr><td>33</td><td>Chipwaza [<xref ref-type="bibr" rid="CR49">49</xref>]</td><td>Morogoro, Tanzania</td><td>March–May and Aug-Oct. 2013</td><td>Cross sectional</td><td>364</td><td>31</td><td>9</td><td>2–13</td><td>Blood smear /IgM and IgG ELISA, PCR</td><td>NM</td></tr><tr><td>34</td><td>Dariano [<xref ref-type="bibr" rid="CR50">50</xref>]</td><td>Bo, Sierra Leone</td><td>2012–2013</td><td>Cross sectional</td><td>1260</td><td>3</td><td>0.2</td><td>All ages</td><td>RDTs/IgM, IgG, NS1 ELISA</td><td>NM</td></tr><tr><td>35</td><td>Kolawole [<xref ref-type="bibr" rid="CR51">51</xref>]</td><td>Ilorin,<break></break>Nigeria</td><td>2016</td><td>Cross sectional</td><td>176</td><td>5</td><td>3</td><td>All ages</td><td>RDT/IgM ELISA, PCR</td><td>DENV2, DENV3, DENV4</td></tr><tr><td>36</td><td>Oyeoro [<xref ref-type="bibr" rid="CR52">52</xref>]</td><td>Ibadan, Nigeria</td><td>Jan-April 2013</td><td>Cross sectional</td><td>188</td><td>19</td><td>10</td><td>All ages</td><td>NM/IgG, IgM, NS1 ELISA</td><td>NM</td></tr><tr><td>37</td><td>Sow [<xref ref-type="bibr" rid="CR53">53</xref>]</td><td>Kedougou, Senegal</td><td>July 2009–March 2013</td><td>Cross sectional</td><td>13,845</td><td>1</td><td>0.01</td><td>All ages</td><td>Blood smear, RDT/ IgM ELISA, PCR</td><td><italic>P. falciparum</italic></td></tr><tr><td>38</td><td>Stolar [<xref ref-type="bibr" rid="CR54">54</xref>]</td><td>Ghana</td><td>2011–2014</td><td>Retrospective analysis</td><td>218</td><td>7</td><td>3</td><td>2–14 years</td><td>RDT/IgM and IgG, ELISA, PCR</td><td><italic>P. falciparum</italic></td></tr><tr><td>39</td><td>Vu [<xref ref-type="bibr" rid="CR55">55</xref>]</td><td>Kenya</td><td>2016</td><td>Cross sectional</td><td>579</td><td>33</td><td>6</td><td>1–17 years</td><td>Blood smear /PCR</td><td>NM</td></tr><tr><td colspan="11">Caribbean</td></tr><tr><td>40</td><td>Serre [<xref ref-type="bibr" rid="CR56">56</xref>]</td><td>Spain,<break></break>Infected in Haiti</td><td>2011</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>27</td><td>Blood smear, PCR/IgM, IgG and NS1 ELISA, PCR</td><td><italic>P. falciparum,</italic> DENV4</td></tr><tr><td colspan="11">Southeast Asia</td></tr><tr><td>41</td><td>Che rahim [<xref ref-type="bibr" rid="CR57">57</xref>]</td><td>Kelantan, Malaysia</td><td>2017</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>59</td><td>Blood smear, PCR/NS1 ELISA</td><td><italic>P. knowlesi</italic></td></tr><tr><td>42</td><td>Chong [<xref ref-type="bibr" rid="CR58">58</xref>]</td><td>Malaysia</td><td>2017</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>59</td><td>Blood smear/NS1 and IgM ELISA</td><td><italic>P. knowlesi</italic></td></tr><tr><td>43</td><td>Issaranggoon [<xref ref-type="bibr" rid="CR59">59</xref>]</td><td>Thailand</td><td>2014</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>11</td><td>Blood smear/ NS1, IgM ELISA</td><td><italic>P. falciparum</italic></td></tr><tr><td>44</td><td>McGready [<xref ref-type="bibr" rid="CR60">60</xref>]</td><td>Thai-Burmese border</td><td>Jan 2004-May 2006</td><td>Cross sectional</td><td>209</td><td>1</td><td>0.5</td><td>Pregnant women</td><td>Blood smear/IgM ELISA, NS1 ELISA</td><td><italic>P. falciparum, P. vivax</italic></td></tr><tr><td>45</td><td>Mueller [<xref ref-type="bibr" rid="CR61">61</xref>]</td><td>(Oun Kouma, Ou Chra, Snoul)<break></break>Rural Cambodia</td><td>Jan 2008- Dec 2010</td><td>Prospective observational study</td><td>1193</td><td>30</td><td>2.5</td><td>7–49 years</td><td>RDT/PCR</td><td><italic>P. falciparum, P. vivax</italic></td></tr><tr><td>46</td><td>Thaha [<xref ref-type="bibr" rid="CR62">62</xref>]</td><td>Surabaya, Indonesia</td><td>Nov 2008</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>NM</td><td>Blood smear/IgM, IgG ELISA</td><td>NM</td></tr><tr><td>47</td><td>Ward [<xref ref-type="bibr" rid="CR63">63</xref>]</td><td>East Timor</td><td>2006</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>7</td><td>Blood smear /IgM ELISA</td><td><italic>P. falciparum</italic></td></tr><tr><td>48</td><td>Yong [<xref ref-type="bibr" rid="CR64">64</xref>]</td><td>Riau Island Indonesia</td><td>2012</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>49</td><td>Blood smear/IgM, NS1 ELISA</td><td><italic>P. falciparum</italic></td></tr><tr><td colspan="11">South America</td></tr><tr><td>49</td><td>Carme [<xref ref-type="bibr" rid="CR65">65</xref>]</td><td>French Guiana</td><td>July 2004-June 2005</td><td>Retrospective analysis</td><td>1723</td><td>17</td><td>1</td><td>NM</td><td>Blood smear/PCR, IgM ELISA, virus isolation</td><td><italic>P. vivax</italic> − 14, <italic>P. falciparum</italic>- 3, DENV3–5, DENV1–1, NM-11</td></tr><tr><td>50</td><td>Epelboin [<xref ref-type="bibr" rid="CR66">66</xref>]</td><td>French Guiana</td><td>2004–2010</td><td>Retrospective matched pair study</td><td>NM</td><td>104</td><td>NA</td><td>All ages</td><td>Blood smear/PCR, NS1, IgM, IgA ELISA</td><td><italic>P. vivax</italic> – 80, <italic>P. falciparum</italic> – 21, <italic>P. vivax</italic> + <italic>P. falciparum</italic> – 3, DENV1–3, DENV2–2, DENV3–5, NM-94</td></tr><tr><td>51</td><td>Lupi [<xref ref-type="bibr" rid="CR67">67</xref>]</td><td>Rio de Janeiro, Brazil</td><td>Apr 2013</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>52</td><td>Blood smear, RDT, PCR/ IgM and NS1 ELISA, PCR</td><td><italic>P. ovale wallikeri</italic></td></tr><tr><td>52</td><td>Magalhaes [<xref ref-type="bibr" rid="CR68">68</xref>]</td><td>Brazilian Amazon<break></break>Manaus<break></break>Brazil</td><td>March 2009 to April 2010</td><td>Retrospective study</td><td>132</td><td>11</td><td>8</td><td>Mean age, 42.7 yrs</td><td>Blood smear, PCR/NS1 ELISA, PCR</td><td><italic>P. vivax</italic> DENV2, DENV3, DENV4</td></tr><tr><td>53</td><td>Magalhaes [<xref ref-type="bibr" rid="CR69">69</xref>]</td><td>Brazilian Amazon<break></break>Manaus<break></break>Brazil</td><td>2009–2011</td><td>Cross-sectional</td><td>1578</td><td>44</td><td>3</td><td>All ages</td><td>Blood smear, PCR/ NS1 ELISA, PCR</td><td><italic>P. vivax</italic></td></tr><tr><td>54</td><td>Mendonca [<xref ref-type="bibr" rid="CR70">70</xref>]</td><td>Brazilian Amazon<break></break>Manaus<break></break>Brazil</td><td>2009–2013</td><td>Prospective observational study</td><td>All febrile patients</td><td>30</td><td>NA</td><td>31.11 median age</td><td>Blood smear, PCR/ IgM and NS1 ELISA</td><td><italic>P. vivax,</italic> DENV4–8, DENV3–1, DENV2–18, DENV1–3</td></tr><tr><td>55</td><td>Santana [<xref ref-type="bibr" rid="CR71">71</xref>]</td><td>Novo Repartimento (Pará), Brazil</td><td>May 2003 to August 2005</td><td>Cross sectional</td><td>111</td><td>2</td><td>2</td><td>> 18 years</td><td>Blood smear/PCR</td><td><italic>P. vivax,</italic> DENV2</td></tr></tbody></table><table-wrap-foot><p>N – sample size, ML/DN - Malaria/Dengue coinfection, ELISA - Enzyme linked immunosorbent assay, NS1 - Dengue non-structural protein − 1, PCR - Polymerase Chain reaction, RDT - rapid diagnostic test, PRNT - Plaque reduction neutralisation test, RMAT - Rapaid malaria antigen test, NM - not mentioned, NA - not applicable</p></table-wrap-foot></table-wrap><table-wrap id="Tab2"><label>Table 2</label><caption><p>Coinfection cases of Dengue and Chikungunya</p></caption><table frame="hsides" rules="groups"><thead><tr><th>S.No.</th><th>Citations</th><th>Place</th><th>Year</th><th>Study design</th><th>N</th><th>Positive for coinfection</th><th>Coinfection (%)</th><th>Age</th><th>Diagnostic test DN/CK</th><th>Remarks</th></tr></thead><tbody><tr><td colspan="11">South Asia</td></tr><tr><td>1.</td><td>Afreen [<xref ref-type="bibr" rid="CR72">72</xref>]</td><td>Delhi,<break></break>India</td><td>2014</td><td>Cross sectional</td><td>87</td><td>9</td><td>10</td><td>All ages</td><td>NS1, IgM, IgG ELISA, PCR/ IgM ELISA, PCR</td><td>DENV2 + CHIKV-5, DENV3 + CHIKV -2, DENV1 + CHIKV-1, DENV1 + DENV2+ CHIKV-1</td></tr><tr><td>2.</td><td>Carey [<xref ref-type="bibr" rid="CR73">73</xref>]</td><td>Vellore,<break></break>India</td><td>1964</td><td>Cross sectional</td><td>477</td><td>8</td><td>2</td><td>All ages</td><td>Virus isolation<break></break>Serological<break></break>Complement fixation and Hemagglutination inhibition assay for both infection</td><td>NM</td></tr><tr><td>3.</td><td>Chahar [<xref ref-type="bibr" rid="CR74">74</xref>]</td><td>Delhi,<break></break>India</td><td>2006</td><td>Cross sectional</td><td>69</td><td>6</td><td>9</td><td>All ages</td><td>PCR/PCR</td><td>DENV1, DENV3, DENV4</td></tr><tr><td>4.</td><td>Galate [<xref ref-type="bibr" rid="CR75">75</xref>]</td><td>Mumbai, Maharashtra</td><td>April 2012-Oct. 2013</td><td>Cross sectional</td><td>200</td><td>19</td><td>10</td><td>13–60</td><td>IgM ELISA/IgM ELISA</td><td>NM</td></tr><tr><td>5.</td><td>Hapuarachchi [<xref ref-type="bibr" rid="CR76">76</xref>]</td><td>Sri Lanka</td><td>2006</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>70</td><td>PCR/PCR</td><td>NM</td></tr><tr><td>6.</td><td>Kalawat [<xref ref-type="bibr" rid="CR77">77</xref>]</td><td>Tirupati,<break></break>India</td><td>2011</td><td>Retrospective analysis</td><td>72</td><td>2</td><td>3</td><td>All ages</td><td>IgM ELISA / IgM ELISA</td><td>NM</td></tr><tr><td>7.</td><td>Kaur [<xref ref-type="bibr" rid="CR78">78</xref>]</td><td>Delhi,<break></break>India</td><td>Aug-Dec. 2016</td><td>Cross sectional</td><td>600</td><td>152</td><td>25</td><td>11–68</td><td>IgM ELISA, NS1 ELISA, PCR/IgM ELISA, PCR</td><td>NM</td></tr><tr><td>8.</td><td>Londhey [<xref ref-type="bibr" rid="CR79">79</xref>]</td><td>Mumbai,<break></break>India</td><td>June 2010–April 2015</td><td>Prospective observational study</td><td>300</td><td>30</td><td>10</td><td>All ages</td><td>IgM ELISA, PCR/ IgM ELISA, PCR</td><td>NM</td></tr><tr><td>9.</td><td>Mørch [<xref ref-type="bibr" rid="CR34">34</xref>]</td><td>Assam, Bihar, Chhattisgarh, Maharashtra, Anantpur, Tamilnadu<break></break>India</td><td>April 2011–November 2012</td><td>Cross sectional</td><td>1564</td><td>25</td><td>1.6</td><td>34 mean age</td><td>IgM, NS1 ELISA/IgM ELISA</td><td>NM</td></tr><tr><td>10.</td><td>Mukherjee [<xref ref-type="bibr" rid="CR80">80</xref>]</td><td>Kolkata,<break></break>India</td><td>July 2014-Oct. 2015</td><td>Cross sectional</td><td>326</td><td>53</td><td>16</td><td>All ages</td><td>IgM and NS1 ELISA, PCR/IgM ELISA, PCR</td><td>DENV2, DENV4</td></tr><tr><td>11.</td><td>Neeraja [<xref ref-type="bibr" rid="CR81">81</xref>]</td><td>Hyderabad, Telangana</td><td>2007</td><td>Cross sectional</td><td>713</td><td>8</td><td>1</td><td>NM</td><td>IgG, IgM, PCR/PCR</td><td>NM</td></tr><tr><td>12.</td><td>Paulo [<xref ref-type="bibr" rid="CR82">82</xref>]</td><td>Potugal,<break></break>Infected in India</td><td>2016</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>65</td><td>PCR/IgM ELISA</td><td>DENV3</td></tr><tr><td>13.</td><td>Rahim [<xref ref-type="bibr" rid="CR83">83</xref>]</td><td>Dhaka, Bangladesh</td><td>2017</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>23 female</td><td>NS1 ELISA/IgM ELISA</td><td>NM</td></tr><tr><td>14.</td><td>Saswat [<xref ref-type="bibr" rid="CR84">84</xref>]</td><td>Khurda, Odisha<break></break>Aurangabad,<break></break>Maharashtra India</td><td>July-Dec. 2013</td><td>Cross sectional</td><td>222</td><td>43</td><td>19</td><td>All ages</td><td>NS1, IgM, IgG ELISA, PCR/IgM ELISA, PCR</td><td>DENV2</td></tr><tr><td>15.</td><td>Shaikh [<xref ref-type="bibr" rid="CR85">85</xref>]</td><td>Karnataka,<break></break>India</td><td>July 2010–June 2013</td><td>Cross sectional</td><td>6554</td><td>532</td><td>8</td><td>NM</td><td>IgM ELISA/IgM ELISA</td><td>NM</td></tr><tr><td>16.</td><td>Schilling [<xref ref-type="bibr" rid="CR86">86</xref>]</td><td>Chennai,<break></break>India</td><td>September 2008</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>25</td><td>NS1, IgM ELISA and IFA/IgM IFA</td><td>NM</td></tr><tr><td>17.</td><td>Taraphdar [<xref ref-type="bibr" rid="CR87">87</xref>]</td><td>West Bengal, India</td><td>2010</td><td>Cross sectional</td><td>550</td><td>68</td><td>12</td><td>All ages</td><td>IgM ELISA, PCR / IgM ELISA, PCR</td><td>DENV2, DENV3</td></tr><tr><td>18.</td><td>Kularatne [<xref ref-type="bibr" rid="CR88">88</xref>]</td><td>Peradeniya, Srilanka</td><td>Dec. 2006-March 2007</td><td>Cross sectional</td><td>54</td><td>3</td><td>5</td><td>15–74</td><td>IgM ELISA, Hemagglutination inhibition/ IgM ELISA, Hemagglutination inhibition</td><td>NM</td></tr><tr><td colspan="11">Africa</td></tr><tr><td>19.</td><td>Baba [<xref ref-type="bibr" rid="CR47">47</xref>]</td><td>Nigeria</td><td>July-Dec. 2008</td><td>Cross sectional</td><td>310</td><td>63</td><td>20</td><td>All ages</td><td>PRNT/PRNT</td><td>NM</td></tr><tr><td>20.</td><td>Caron [<xref ref-type="bibr" rid="CR89">89</xref>]</td><td>Gabon</td><td>Sep 2007-Aug 2010</td><td>Cross sectional</td><td>4287</td><td>37</td><td>1</td><td>All ages</td><td>PCR of partial E gene/ PCR of partial E1 gene</td><td>DENV2</td></tr><tr><td>21.</td><td>Dariano [<xref ref-type="bibr" rid="CR50">50</xref>]</td><td>Bo, Sierra Leone</td><td>2012–2013</td><td>Cross sectional</td><td>1260</td><td>13</td><td>1</td><td>All ages</td><td>IgM, IgG, NS1 ELISA/IgM ELISA</td><td>NM</td></tr><tr><td>22.</td><td>Leroy [<xref ref-type="bibr" rid="CR90">90</xref>]</td><td>Gabon</td><td>March–July 2007</td><td>Cross sectional</td><td>773</td><td>8</td><td>1</td><td>NM</td><td>PCR/ PCR</td><td>DENV2</td></tr><tr><td>23.</td><td>Nkoghe [<xref ref-type="bibr" rid="CR91">91</xref>]</td><td>Franceville, Gabon</td><td>Feb-July 2010</td><td>Cross sectional</td><td>433</td><td>20</td><td>4.6</td><td>1–77</td><td>PCR/PCR</td><td>NM</td></tr><tr><td>24.</td><td>Parreira [<xref ref-type="bibr" rid="CR92">92</xref>]</td><td>Portugal, infected in Luanda, Angola</td><td>January 2014</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>Early 50s</td><td>NS1 IgM, IgG ELISA, PCR/IgM ELISA, PCR</td><td>DENV4</td></tr><tr><td>25.</td><td>Ratsitorahina [<xref ref-type="bibr" rid="CR93">93</xref>]</td><td>Tomasina,<break></break>Madagascar</td><td>Jan-March 2006</td><td>Cross sectional</td><td>55</td><td>10</td><td>18</td><td>NM</td><td>IgM ELISA, PCR/IgM ELISA, PCR</td><td>DENV1</td></tr><tr><td colspan="11">Caribbean</td></tr><tr><td>26.</td><td>Edwards [<xref ref-type="bibr" rid="CR94">94</xref>]</td><td>Guatemala</td><td>June 2015</td><td>Surveillance report</td><td>144</td><td>46</td><td>32</td><td>All ages</td><td>PCR/ PCR</td><td>DENV1–4, DENV2–40, DENV4–2</td></tr><tr><td>27.</td><td>Omarjee [<xref ref-type="bibr" rid="CR95">95</xref>]</td><td>Island of Saint Martin</td><td>Dec. 2013-<break></break>Jan 2014</td><td>Cross sectional</td><td>1502</td><td>16</td><td>1</td><td>All ages</td><td>IgM, IgG ELISA and PCR / IgM, IgG ELISA and PCR</td><td>DENV1–10, DENV2–2, DENV4–4</td></tr><tr><td colspan="11">Southeast Asia</td></tr><tr><td>28.</td><td>Cha [<xref ref-type="bibr" rid="CR96">96</xref>]</td><td>Osong korea Infected (2 in Philllipine, 1 Vietnam, 1 Indonesia, 1 East Timor)</td><td>2009–2010</td><td>Cross sectional</td><td>486</td><td>5</td><td>1</td><td>11–70</td><td>IgM ELISA, PCR/ IgM ELISA, PCR</td><td>NM</td></tr><tr><td>29.</td><td>Chang [<xref ref-type="bibr" rid="CR97">97</xref>]</td><td>Taipei China, infected in Singapore</td><td>2009 April</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>12</td><td>IgM and IgG ELISA, PCR/ IgM and IgG ELISA, PCR</td><td>DENV2</td></tr><tr><td>30.</td><td>Khai Ming [<xref ref-type="bibr" rid="CR98">98</xref>]</td><td>Rangoon, Burma</td><td>July 1970-Dec. 1972</td><td>Cross sectional</td><td>2060</td><td>55</td><td>2.6</td><td>0–11</td><td>HI, CF/HI, CF</td><td>NM</td></tr><tr><td>31.</td><td>Laoprasopwattana [<xref ref-type="bibr" rid="CR99">99</xref>]</td><td>Southern Thailand</td><td>April–July 2009</td><td>Prospective Cohort study</td><td>50</td><td>1</td><td>2</td><td>≤15</td><td>IgM ELISA and Hemagglutination inhibition/IgM IFA, PCR</td><td>NM</td></tr><tr><td>32.</td><td>Nayar [<xref ref-type="bibr" rid="CR100">100</xref>]</td><td>Kinta,<break></break>Malaysia</td><td>2006</td><td>Case report</td><td>2</td><td>2</td><td>NA</td><td>22 and 28</td><td>NS1, IgM ELISA, PCR/PCR</td><td>DENV1</td></tr><tr><td>33.</td><td>Ooi [<xref ref-type="bibr" rid="CR101">101</xref>]</td><td>Selangor, Malaysia,</td><td>2009</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>NM</td><td>NM/Complete Genome sequencing of CHIKV</td><td>DENV2</td></tr><tr><td>34.</td><td>Phommanivong [<xref ref-type="bibr" rid="CR102">102</xref>]</td><td>Champasak Laos</td><td>July-Aug 2013</td><td>Cross sectional</td><td>40</td><td>5</td><td>12.5</td><td>5–65</td><td>PCR/PCR</td><td>DENV2–3,<break></break>DENV3–2</td></tr><tr><td>35.</td><td>Tun [<xref ref-type="bibr" rid="CR103">103</xref>]</td><td>Mandalay,<break></break>Myanmar</td><td>July–October 2010</td><td>Cross sectional</td><td>116</td><td>7</td><td>6</td><td>≤12</td><td>IgM ELISA, PCR/IgM ELISA, PCR</td><td>NM</td></tr><tr><td colspan="11">North America</td></tr><tr><td>36.</td><td>Kariyawasam [<xref ref-type="bibr" rid="CR104">104</xref>]</td><td>Toronto, Canada</td><td>May 2006-April 2007 and Feb 2013-March 2014</td><td>Retrospective analysis</td><td>1304</td><td>1</td><td>0.07</td><td>0–91</td><td>PCR/PCR</td><td>DENV-1</td></tr><tr><td>37.</td><td>Lindholm [<xref ref-type="bibr" rid="CR105">105</xref>]</td><td>Maryland,<break></break>USA</td><td>Dec 2013-May 2015</td><td>Cross sectional</td><td>267</td><td>2</td><td>0.7</td><td>25–60</td><td>IgM, IgG ELISA, PCR, PRNT/ IgM, IgG ELISA, PCR, PRNT</td><td>NM</td></tr><tr><td colspan="11">South America</td></tr><tr><td>38.</td><td>Bocanegra [<xref ref-type="bibr" rid="CR106">106</xref>]</td><td>Barcelona Spain Infected in south America</td><td>April 2014–2015</td><td>Retrospective</td><td>42</td><td>5</td><td>12</td><td>34.6 mean age</td><td>IgM ELISA/IgM ELISA, PCR</td><td>NM</td></tr><tr><td>39.</td><td>Brooks [<xref ref-type="bibr" rid="CR107">107</xref>]</td><td>Santos,<break></break>Brazil</td><td>2017</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>27</td><td>IgM ELISA/IgM ELISA</td><td>NM</td></tr><tr><td>40.</td><td>Calvo [<xref ref-type="bibr" rid="CR108">108</xref>]</td><td>Girardot,<break></break>Colombia</td><td>Feb 2015</td><td>Cross sectional</td><td>8</td><td>4</td><td>50</td><td>0–10</td><td>IgM ELISA, PCR/PCR</td><td>NM</td></tr><tr><td>41.</td><td>Carrillo-Hernández [<xref ref-type="bibr" rid="CR109">109</xref>]</td><td>Norte de Santander, Colombia</td><td>August 2015 – April 2016</td><td>Cross sectional</td><td>157</td><td>12</td><td>7.6</td><td>26.81</td><td>PCR/PCR</td><td>NM</td></tr><tr><td>42.</td><td>Farrell [<xref ref-type="bibr" rid="CR110">110</xref>]</td><td>Machala, Ecuador</td><td>2015</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>35</td><td>IgM, IgG ELISA/PCR</td><td>NM</td></tr><tr><td>43.</td><td>Gomez-Govea [<xref ref-type="bibr" rid="CR111">111</xref>]</td><td>Nuevo leon,<break></break>Mexico</td><td>Jan-Oct 2015</td><td>Cross sectional</td><td>101</td><td>5</td><td>5</td><td>31 median age</td><td>IgM ELISA/IgM ELISA, PCR</td><td>NM</td></tr><tr><td>44.</td><td>Mercado [<xref ref-type="bibr" rid="CR112">112</xref>]</td><td>Bogota, Colombia</td><td>Sept 2014-Oct 2015</td><td>Retrospective analysis</td><td>58</td><td>7</td><td>12</td><td>NM</td><td>IgM ELISA, PCR/PCR</td><td>NM</td></tr><tr><td>45.</td><td>Rosso [<xref ref-type="bibr" rid="CR113">113</xref>]</td><td>Cali,<break></break>Colombia</td><td>2015</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>72</td><td>PCR/ PCR</td><td>DENV3</td></tr><tr><td colspan="11">Middle East</td></tr><tr><td>46.</td><td>Malik [<xref ref-type="bibr" rid="CR114">114</xref>]</td><td>Al-Hudaydah, Yemen</td><td>Oct 2010-March 2011</td><td>Cross sectional</td><td>136</td><td>1</td><td>0.7</td><td>NM</td><td>IgM ELISA, PCR/IgM ELISA</td><td>NM</td></tr><tr><td>47.</td><td>Rezza [<xref ref-type="bibr" rid="CR115">115</xref>]</td><td>Al-Hudaydah<break></break>Yemen</td><td>2012</td><td>Cross sectional</td><td>400</td><td>14</td><td>3.5</td><td>All ages</td><td>IgM, IgG ELISA and PCR/ IgM, IgG ELISA and PCR</td><td>DENV2 Predominantly</td></tr></tbody></table><table-wrap-foot><p>N – sample size, DN/CK – Dengue/Chikungunya coinfection, ELISA – Enzyme linked immunosorbent assay, NS1 - Dengue non-structural protein −1, PCR – Polymerase Chain reaction, IFA – immunofluorescence assay, PRNT – Plaque reduction neutralisation test, NM – not mentioned, NA – not applicable</p></table-wrap-foot></table-wrap><table-wrap id="Tab3"><label>Table 3</label><caption><p>Coinfection cases of Malaria and Chikungunya</p></caption><table frame="hsides" rules="groups"><thead><tr><th>S.No.</th><th>Citations</th><th>Place</th><th>Year</th><th>Study design</th><th>N</th><th>Positive for coinfection</th><th>Coinfection(%)</th><th>Age</th><th>Diagnostic test ML/CK</th><th>Remarks</th></tr></thead><tbody><tr><td colspan="11">South Asia</td></tr><tr><td>1.</td><td>Mørch [<xref ref-type="bibr" rid="CR34">34</xref>]</td><td>Assam, Bihar, Chhattisgarh, Maharashtra, Anantpur, Tamilnadu</td><td>April 2011–Nov 2012</td><td>Cross sectional</td><td>1564</td><td>20</td><td><bold>1.3</bold></td><td>34 mean age</td><td>IgM, NS1 ELISA/IgM ELISA</td><td>NM</td></tr><tr><td colspan="11">Africa</td></tr><tr><td>2.</td><td>Ayorinde [<xref ref-type="bibr" rid="CR46">46</xref>]</td><td>Ogun, Nigeria</td><td>April-May 2014</td><td>Cross sectional</td><td>60</td><td>9</td><td>15</td><td>All ages</td><td>Blood smear, RDT, PCR/IgM ELISA</td><td><italic>P. falciparum</italic></td></tr><tr><td>3.</td><td>Baba [<xref ref-type="bibr" rid="CR47">47</xref>]</td><td>Nigeria</td><td>July-Dec. 2008</td><td>Cross sectional</td><td>310</td><td>21</td><td>6.7</td><td>All ages</td><td>Blood smear /PRNT</td><td><italic>P. falciparum</italic></td></tr><tr><td>4.</td><td>Chipwaza [<xref ref-type="bibr" rid="CR49">49</xref>]</td><td>Morogoro, Tanzania</td><td>March–May and Aug-Oct. 2013</td><td>Cross sectional</td><td>364</td><td>2</td><td>0.6</td><td>2–13 years</td><td>Blood smear / IgM and IgG ELISA,</td><td>NM</td></tr><tr><td>5.</td><td>Dariano [<xref ref-type="bibr" rid="CR50">50</xref>]</td><td>Bo, Sierra Leone</td><td>2012–2013</td><td>Cross sectional</td><td>1260</td><td>118</td><td>9</td><td>All ages</td><td>RDTs/IgM ELISA</td><td>NM</td></tr><tr><td>6.</td><td>Mugabe [<xref ref-type="bibr" rid="CR116">116</xref>]</td><td>Quelimane Mozambique</td><td>Feb-June 2016</td><td>Cross Sectional</td><td>163</td><td>2</td><td>1.2</td><td>28 median age</td><td>RDT /IgM ELISA, PCR</td><td>NM</td></tr><tr><td>7.</td><td>Sow [<xref ref-type="bibr" rid="CR53">53</xref>]</td><td>Kedougou, Senegal</td><td>July 2009–March 2013</td><td>Cross sectional</td><td>13,845</td><td>3</td><td>0.02</td><td>All ages</td><td>Blood smear, RDT/ IgM ELISA, PCR</td><td><italic>P. falciparum</italic></td></tr></tbody></table><table-wrap-foot><p>N – sample size, ML/CK- Malaria/Chikungunya coinfection, ELISA – Enzyme linked immunosorbent assay, NS1 - Dengue non-structural protein −1, PCR – Polymerase Chain reaction, RDT – rapid diagnostic test, PRNT – Plaque reduction neutralisation test, NM – not mentioned</p></table-wrap-foot></table-wrap><table-wrap id="Tab4"><label>Table 4</label><caption><p>Coinfection cases of Malaria, Dengue and Chikungunya</p></caption><table frame="hsides" rules="groups"><thead><tr><th>S.No.</th><th>Citations</th><th>Place</th><th>Year</th><th>Study design</th><th>N</th><th>Positive for coinfection</th><th>Coinfection (%)</th><th>Age</th><th>Diagnostic test ML/DN/CK</th><th>Remarks</th></tr></thead><tbody><tr><td colspan="11">South Asia</td></tr><tr><td>1.</td><td>Abdullah [<xref ref-type="bibr" rid="CR117">117</xref>]</td><td>Delhi,<break></break>India</td><td>2016</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>21</td><td>Blood smear, RDT/PCR/IgM ELISA, PCR</td><td><italic>P. vivax,</italic> DENV3</td></tr><tr><td>2.</td><td>Gupta [<xref ref-type="bibr" rid="CR118">118</xref>]</td><td>Delhi,<break></break>India</td><td>2017</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>55</td><td>RDT/NS1, IgM ELISA/PCR</td><td><italic>P. falciparum</italic></td></tr><tr><td>3.</td><td>Mørch [<xref ref-type="bibr" rid="CR34">34</xref>]</td><td>Assam, Bihar, Chhattisgarh, Maharashtra, Anantpur, Tamilnadu India</td><td>April 2011–Nove 2012</td><td>Cross sectional</td><td>1564</td><td>2</td><td>0.1</td><td>34 mean age</td><td>Blood smear/IgM, NS1 ELISA/IgM ELISA</td><td>NM</td></tr><tr><td>4.</td><td>Tazeen [<xref ref-type="bibr" rid="CR119">119</xref>]</td><td>Delhi,<break></break>India</td><td>2016</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>3</td><td>Blood smear /PCR/PCR</td><td><italic>P. vivax</italic></td></tr><tr><td colspan="11">Africa</td></tr><tr><td>5.</td><td>Dariano [<xref ref-type="bibr" rid="CR50">50</xref>]</td><td>Bo, Sierra Leone</td><td>2012–2013</td><td>Cross sectional</td><td>1260</td><td>4</td><td>0.3</td><td>All ages</td><td>RDTs/IgM, IgG, NS1 ELISA/IgM ELISA</td><td>NM</td></tr><tr><td>6.</td><td>Raut [<xref ref-type="bibr" rid="CR120">120</xref>]</td><td>India<break></break>Infected in Nigeria</td><td>2014</td><td>Case report</td><td>1</td><td>1</td><td>NA</td><td>21</td><td>Blood smear / NS1 ELISA, PCR/PCR</td><td><italic>P. falciparum</italic></td></tr></tbody></table><table-wrap-foot><p>N – sample size, ML/DN/CK – Malaria/Dengue/Chikungunya coinfection, ELISA – Enzyme linked immunosorbent assay, NS1 - Dengue non-structural protein −1, PCR – Polymerase Chain reaction, RDT – rapid diagnostic test, NA – not applicable, NM-not mentioned</p></table-wrap-foot></table-wrap></p><p id="Par19">Out of the 55 reports about Malaria/Dengue coinfections, only ten have reported the serotype of the Dengue virus. Out of the 47 reports about Dengue/Chikungunya coinfections 20 reports have mentioned the serotype of Dengue virus. Earliest report of Malaria/Dengue coinfection came in 2003 from Brazil, while earliest reported case of Dengue/Chikungunya coinfection came in 1964 from India. Malaria/Chikungunya cases were reported as late as 2008 from Nigeria. A retrospective matched pair study from French Guiana reported most cases (104) of Malaria/Dengue coinfections. Maximum cases of Dengue/Chikungunya coinfections (532) were reported from Karnataka in India and most cases of Malaria/Chikungunya coinfections (118) were reported from Bo, Sierra Leone.</p><p id="Par20">Most cases of coinfections were reported from South Asia (52), primarily from India, followed by Africa (25), South-east Asia (16), South America (15), Caribbean (3) and Middle East (2). Two studies from North America reported coinfections of Dengue/Chikungunya in returning travellers without identifying the location where coinfections occurred. Malaria/Dengue coinfections were reported from 44 unique locations spread across 20 different countries (Fig. <xref rid="Fig2" ref-type="fig">2</xref>). Dengue/Chikungunya coinfections were reported from 48 unique locations spread across 26 countries (Fig. <xref rid="Fig3" ref-type="fig">3</xref>). 5 countries from African continent and India reported cases of Malaria/Chikungunya coinfections (Fig. <xref rid="Fig4" ref-type="fig">4</xref>). Cases of Malaria/Dengue/Chikungunya coinfections were reported from India, Sierra Leone and Nigeria (Fig. <xref rid="Fig5" ref-type="fig">5</xref>). Seven countries reported infection in returning travellers(Fig. <xref rid="Fig6" ref-type="fig">6</xref>). Based upon cross sectional studies Malaria/ Dengue prevalence varied widely, ranging between 0.1–23% from south Asia, 0.01–9% from Africa, 0.5–2.5% from Southeast Asia and 1–3% from South America. The frequency of Dengue/Chikungunya coinfections ranged from 1 to 25% from South Asia, 1–20% from Africa, 1–32% from Caribbean, 1–12.5% from Southeast Asia, 0.07–0.7% from North America, 5–50% from South America and 0.7–3.5% from Middle east. Malaria/Chikungunya coinfections frequency ranged from 0.02–15% from Africa and a single study reported from India reported 1.3% patients coinfected with both pathogens. Malaria/Dengue/Chikungunya coinfection frequency was reported by two cross sectional studies, one from India with 0.1% prevalence and another from Sierra Leone with 0.3% prevalence.<fig id="Fig2"><label>Fig. 2</label><caption><p>Global distribution of Malaria/Dengue coinfections</p></caption><graphic xlink:href="12889_2018_5626_Fig2_HTML" id="MO2"></graphic></fig><fig id="Fig3"><label>Fig. 3</label><caption><p>Global distribution of Dengue/Chikungunya coinfections</p></caption><graphic xlink:href="12889_2018_5626_Fig3_HTML" id="MO3"></graphic></fig><fig id="Fig4"><label>Fig. 4</label><caption><p>Global distribution of Malaria/Chikungunya coinfections</p></caption><graphic xlink:href="12889_2018_5626_Fig4_HTML" id="MO4"></graphic></fig><fig id="Fig5"><label>Fig. 5</label><caption><p>Global distribution of Malaria/Dengue/Chikungunya coinfections</p></caption><graphic xlink:href="12889_2018_5626_Fig5_HTML" id="MO5"></graphic></fig><fig id="Fig6"><label>Fig. 6</label><caption><p>Countries from where coinfection cases were reported in returning travellers</p></caption><graphic xlink:href="12889_2018_5626_Fig6_HTML" id="MO6"></graphic></fig></p></sec><sec id="Sec8"><title>Discussion</title><p id="Par21">Malaria, Dengue and Chikungunya are arthropod borne diseases that have shared endemic profiles. These diseases are spread by mosquito vector, which are found in abundance in tropical regions of the world. <italic>Anopheles</italic> mosquito, which transmits Malaria parasite, is a night biting mosquito and breed in stagnant water [<xref ref-type="bibr" rid="CR121">121</xref>]. <italic>Aedes</italic> that spreads Dengue and Chikungunya, on the other hand bites in daylight and breeds in stored clean water [<xref ref-type="bibr" rid="CR122">122</xref>]. Expansion of the <italic>Aedes</italic> vector has lead to introduction of Dengue and Chikungunya to newer locations. Rapid urbanisation without the development of civic infrastructure, constant movement of population for livelihood, monsoon dependent breeding patterns and overlapping habitats have lead to co-circulation and coinfection of these pathogens in the same population [<xref ref-type="bibr" rid="CR123">123</xref>]. Diagnosis of cases of coinfection is compounded by the fact that initial symptoms of all three diseases are very similar that include febrility as the common factor. Several reports have been published that does not identify the coinfecting pathogen due to lack of distinguishing symptoms at the time, but retrospective analysis later revealed otherwise. In resource poor settings and during outbreaks clinicians might not have the resources or time to rely on detailed investigations.</p><p id="Par22">We have attempted to identify regions of the world from where cases of mixed infection with Malaria, Dengue and Chikungunya have been reported. We searched the databases to identify published reports about any of these coinfections. Most reports of Malaria/Dengue and Dengue/Chikungunya coinfections were reported from India. In recent years there have been many outbreaks of Dengue and Chikungunya in India, not to mention that the first published report of Dengue/Chikungunya coinfection was reported from India in 1967 [<xref ref-type="bibr" rid="CR72">72</xref>]. However the overall percentage of Malaria/Dengue coinfections was low which, can be explained by different vector species for Malaria verses Dengue and Chikungunya. The highest frequency of Malaria/Dengue coinfections was reported from Pakistan that is endemic for both Malaria and Dengue. Lowest frequency was reported form Senegal with only 0.01%. 41 reports clearly identified the parasite species for Malaria infection but only 10 reported the serotype of Dengue virus. All four serotypes were found to exist with Malaria parasite. Coinfection cases were found in all age groups and gender. Nearly 85% of the reports for Malaria/Dengue coinfections have used microscopic confirmation of the Malaria parasite identifying the parasite load and species. Dengue infections were primarily detected by a combination of immunoglobulin ELISA, NS1 ELISA and PCR.</p><p id="Par23">Dengue/Chikungunya coinfections were reported by 47 studies and an overall higher percentage as compared to Malaria/Dengue coinfection possibly because of similar vector species. The Highest frequency of Dengue/Chikungunya coinfections was reported from Colombia and lowest from Canada in returning travellers. Dengue virus serotype-4 was the predominant serotype found in cases of coinfections. Malaria/Chikungunya coinfections were rare with only 7 published reports. All of them were reported from Africa and India. 6 studies reported Malaria/Dengue/Chikungunya coinfections, four of them were case reports and two cross sectional studies. Three of the case reports were infected in Delhi while another one could have been infected in Nigeria or India. Delhi has become a hub of Industrial and social activities with a burgeoning population. Almost every year during monsoon season the city witnesses Dengue outbreaks with thousands of people getting infected. Due to the lack of distinguishing clinical features, laboratory diagnosis based on endemic patterns and outbreak reports are the only way for adequate clinical management of double or triple coinfections. At least 12 studies reported coinfections in returning travellers underlining the role of travel-based spread of the diseases. This phenomenon has been observed for SARS, MERS-CoV and Dengue [<xref ref-type="bibr" rid="CR124">124</xref>–<xref ref-type="bibr" rid="CR126">126</xref>]. Exposing a naïve population to new pathogens might lead to disease outbreak, not to mention viral mutations to adapt its human or mosquito host resulting in more pathogenic strain. Travel advisories and routine surveillance of returning travelers to endemic regions should be implemented stringently to control spread of infections.</p><p id="Par24">Interaction of multiple pathogens within a host may potentially result in several different outcomes. Firstly, if the coinfecting organisms are dependent on similar tissues, the host may have to deal with multiple pathogens at the same time and place. Such interactions are likely to be detrimental to the host as happens in the case of coinfection with Hepatitis B, C and Delta virus coinfections. Hepatitis B, C and Delta virus coinfections results in severe chronic disease that responds poorely to the interferon alpha treatment [<xref ref-type="bibr" rid="CR127">127</xref>] as compared to single infections. Secondly, the immune effector mechanisms triggered by one pathogen may weaken or divert the host immunity leading to severe outcomes or increased resistance to therapy as exemplified in the case of infection with <italic>Mycobacterium tuberculosis</italic> and parasite coinfections [<xref ref-type="bibr" rid="CR128">128</xref>]. Thirdly, the coinfection may not have any serious effect on the prognosis of disease. However, even in such cases the misdiagnosis and mistreatment that may result, can be detrimental to the host. And finally, a coinfection may infact lead to better prognosis. For instance, it has been observed in the decreased mortality rate among the HIV patients coinfected with hepatitis G virus as compared to patients infected with HIV [<xref ref-type="bibr" rid="CR129">129</xref>]. <italic>Plasmodium</italic>, Dengue virus and Chikungunya virus all infect different cell types in humans and might influence immune effector mechanism by downregulationg proinflammaotry cytokines like IL-12 and IFN-γ [<xref ref-type="bibr" rid="CR11">11</xref>, <xref ref-type="bibr" rid="CR130">130</xref>]. A proper clinical analysis of Malaria, Dengue and Chikungunya coinfection is necessary to form an informed opinion on following a treatment regimen that best supports the patient and leads to an early resolution of the infection. Out of 104 reports, there are very few reports that have actually looked at the disease severity by establishing proper controls and comparing it with cases of monoinfections systematically. For Malaria/Dengue coinfections, prolonged fever, thrombocytopenia, anemia, renal failure and Jaundice were more pronounced as compared to monoinfections. Dengue/Chikungunya coinfections can result in diarrahea, deep bleeding, hepatomegaly and overall increase in disease severity. High grade fever was the only distinguishing feature of Malaria/Chikungunya coinfection. More such studies are required to create a consensus about disease outcome in cases of coinfections. Animal models that can replicate the coinfection scenario would be very helpful in identifying severity patterns for these diseases.</p><p id="Par25">The distribution of <italic>Aedes</italic> vector has been reported from Southeast Asia, South Asia, East, Central and West Africa, Caribbean and South America. <italic>Aedes aegypti</italic> and <italic>Aedes albopictus</italic> are responsible for the spread of Dengue, Chikungunya, West Nile, Yellow fever and Zika virus [<xref ref-type="bibr" rid="CR131">131</xref>]. It is difficult to distinguish whether cases of coinfection are due to separate mosquito bites delivering the viruses or single bite by mosquito harboring both viruses. The incubation period of both viruses is nearly same so both diseases are manifested around the same time. <italic>Anopheles</italic> has also been reported from the above-mentioned regions and also from East and central Asia, Europe and North America [<xref ref-type="bibr" rid="CR132">132</xref>]. Most cases of Malaria/Dengue and Malaria/Chikungunya coinfections were found from the regions where both vector species are present. In many instances a seasonal pattern of infections is observed with most cases being reported during monsoon season, which coincides with the breeding season of Mosquito vector. Climatic, sociodemographic and environmental factor play a crucial role in survivability and distribution of the mosquito vector thereby influencing cases of coinfections [<xref ref-type="bibr" rid="CR133">133</xref>]. Vector control continues to be an integral part of reducing disease burden but very few studies reported about the vectors responsible for cases of coinfection. Routine collection of vector surveillance data and thorough analysis of the role of vectors in coinfection cases need to be assessed.</p><p id="Par26">Data collection is prone to bias, to this affect we have made every effort to search and analyze the current literature with broad search queries, nonetheless many relevant studies were unavailable due to lack of full text availability. Also the review relied completely on published literature where grey literature and studies with minimal or negative results may not have been included resulting in publication bias. Furthermore, studies obtained were of variable quality and many did not reported data on disease severity and outcomes in cases of coinfections. Despite these lacunas, the present study attempts to clearly identify regions of the world from where cases of coinfections were reported by thorough search and analysis of published reports. Our analysis indicates that coinfections with Malaria, Dengue and Chikungunya or in rare instances all three is a possibility. Our analysis also indicates that there are higher percentages of people with febrile symptoms, which might have Dengue/Chikungunya coinfections as compared to Malaria/Dengue or Malaria/Chikungunya coinfections. Shared epidemiology, vector distribution and co-circulation of pathogens are some of the reasons for coinfections. We have georeferenced cases of coinfections and identified affected countries of the worlds, establishing co-endemicity of these infections, which might help in proper and complete diagnosis of cases of coinfections with similar initial symptoms.</p></sec><sec id="Sec9"><title>Conclusion</title><p id="Par27">This systematic review has found evidence of Malaria, Dengue and Chikungunya coinfections in 42 Countries spread across several geographical locations. Malaria/Dengue was the most prevalent coinfection followed by Dengue/Chikungunya. These infections often affect same populations due to share endemicity and can be present simultaneously in the same individual. Similar initial symptoms make it harder for clinicians to identify cases of coinfections. Most coinfections were found from South Asia and Africa. <italic>P. falciparum</italic> and <italic>P. vivax</italic> were the most common malaria species found with coinfecting arbovirus and DENV-4 was the most common serotype found in cases of Dengue coinfections. Prolonged and high grade fever, thrombocytopenia, diarrhea, Jaundice and hepatomegaly were some of the signs and symptoms associated with cases of coinfection. We also found evidence of coinfections in returning travellers, which have the potential to introduce the pathogen into new locations with established vector populations. Our study highlights the global prevalence of cases of coinfection and their geographical distribution, which could help in systematic planning, surveillance, diagnosis and health care delivery to the affected population.</p></sec><sec sec-type="supplementary-material"><title>Additional file</title><sec id="Sec10"><p><supplementary-material content-type="local-data" id="MOESM1"><media xlink:href="12889_2018_5626_MOESM1_ESM.docx"><label>Additional file 1:</label><caption><p><bold>Table S1.</bold> Detailed search strategy. (DOCX 14 kb)</p></caption></media></supplementary-material></p></sec></sec></body><back><glossary><title>Abbreviations</title><def-list><def-item><term>CHIKV</term><def><p id="Par5">Chikungunya Virus</p></def></def-item><def-item><term>DENV</term><def><p id="Par6">Dengue Virus</p></def></def-item><def-item><term>ELISA</term><def><p id="Par7">Enzyme linked immunosorbent assay</p></def></def-item><def-item><term>MERS-CoV</term><def><p id="Par8">Middle East respiratory syndrome corona virus</p></def></def-item><def-item><term>PCR</term><def><p id="Par9">Polymerase chain reaction</p></def></def-item><def-item><term>SARS</term><def><p id="Par10">Severe Acute Respiratory Syndrome</p></def></def-item></def-list></glossary><fn-group><fn><p><bold>Electronic supplementary material</bold></p><p>The online version of this article (10.1186/s12889-018-5626-z) contains supplementary material, which is available to authorized users.</p></fn></fn-group><ack><title>Availability of data and materials</title><p>The datasets analysed during the current study is available from the corresponding author on reasonable request.</p></ack><notes notes-type="author-contribution"><title>Authors’ contributions</title><p>NS, SM, AH, extracted the data, AAC, FD and SP cross checked and tabulated the data, NS wrote the manuscript. 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