Efficacy of co-administered diethylcarbamazine and albendazole against adult Wuchereria bancrofti
Identifieur interne : 000394 ( Istex/Corpus ); précédent : 000393; suivant : 000395Efficacy of co-administered diethylcarbamazine and albendazole against adult Wuchereria bancrofti
Auteurs : Gerusa Dreyer ; David Addiss ; John Williamson ; Joaquim Nor EsSource :
- Transactions of The Royal Society of Tropical Medicine and Hygiene [ 0035-9203 ] ; 2006-12.
English descriptors
- KwdEn :
Abstract
Although diethylcarbamazine (DEC) and albendazole are recommended to interrupt transmission of Wuchereria bancrofti, little is known about the macrofilaricidal effect of this drug combination. Forty-seven men with W. bancrofti infection were randomly assigned to receive a single dose of either DEC alone (6 mg/kg) (n = 25) or a combination of DEC (6 mg/kg) and albendazole (400 mg) (n = 22). Physical examinations for scrotal nodules (resulting from worm death) and ultrasound examinations (to detect living adult worms) were performed before treatment and 7, 14, 30, 45, 60, 90, 180, 270 and 360 days after treatment. Blood was examined for microfilariae before and 30 days and 360 days after treatment. Seven days post treatment, intrascrotal nodules were detected at the site of 21 (46.7%) adult worm nests in men who received DEC alone compared with 2 (6.1%) sites in men who received DEC and albendazole (P = 0.002). One year after treatment, 10 (22.2%) original adult worm nests remained detectable by ultrasound among men who received DEC alone compared with 18/32 (56.3%) nests among men who received both drugs (P = 0.016). Microfilaraemia prevalence and density decreased to a similar extent in both groups. Addition of albendazole appeared to decrease the macrofilaricidal effect of DEC against W. bancrofti, with no detectable enhancement in microfilarial suppression.
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DOI: 10.1016/j.trstmh.2006.04.006
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ISTEX:08BDB13FA4F7E3873CC5F56ADC64278EFCC04AA2Le document en format XML
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Prof. Moraes Rego s/n, Cidade Universitária, CEP 50740-900, Recife PE, Brazil</mods:affiliation></affiliation><affiliation><mods:affiliation>Centro do Pesquisas Aggeu Magalhaes, FIOCRUZ, Recife PE, Brazil</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: dreyer-g@uol.com.br</mods:affiliation></affiliation></author><author><name sortKey="Addiss, David" sort="Addiss, David" uniqKey="Addiss D" first="David" last="Addiss">David Addiss</name><affiliation><mods:affiliation>Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA</mods:affiliation></affiliation></author><author><name sortKey="Williamson, John" sort="Williamson, John" uniqKey="Williamson J" first="John" last="Williamson">John Williamson</name><affiliation><mods:affiliation>Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA</mods:affiliation></affiliation></author><author><name sortKey="Nor Es, Joaquim" sort="Nor Es, Joaquim" uniqKey="Nor Es J" first="Joaquim" last="Nor Es">Joaquim Nor Es</name><affiliation><mods:affiliation>NEPAF, Hospital das Clínicas, Universidade Federal de Pernambuco, Av. 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Prof. Moraes Rego s/n, Cidade Universitária, CEP 50740-900, Recife PE, Brazil</mods:affiliation></affiliation><affiliation><mods:affiliation>Centro do Pesquisas Aggeu Magalhaes, FIOCRUZ, Recife PE, Brazil</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: dreyer-g@uol.com.br</mods:affiliation></affiliation></author><author><name sortKey="Addiss, David" sort="Addiss, David" uniqKey="Addiss D" first="David" last="Addiss">David Addiss</name><affiliation><mods:affiliation>Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA</mods:affiliation></affiliation></author><author><name sortKey="Williamson, John" sort="Williamson, John" uniqKey="Williamson J" first="John" last="Williamson">John Williamson</name><affiliation><mods:affiliation>Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA</mods:affiliation></affiliation></author><author><name sortKey="Nor Es, Joaquim" sort="Nor Es, Joaquim" uniqKey="Nor Es J" first="Joaquim" last="Nor Es">Joaquim Nor Es</name><affiliation><mods:affiliation>NEPAF, Hospital das Clínicas, Universidade Federal de Pernambuco, Av. Prof. Moraes Rego s/n, Cidade Universitária, CEP 50740-900, Recife PE, Brazil</mods:affiliation></affiliation><affiliation><mods:affiliation>Departmento de Cirurgia, Hospital das Clínicas, Universidade Federal de Pernambuco, Recife PE, Brazil</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Transactions of The Royal Society of Tropical Medicine and Hygiene</title><title level="j" type="abbrev">Trans R Soc Trop Med Hyg</title><idno type="ISSN">0035-9203</idno><idno type="eISSN">1878-3503</idno><imprint><publisher>Royal Society of Tropical Medicine and Hygiene</publisher><date type="published" when="2006-12">2006-12</date><biblScope unit="volume">100</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="1118">1118</biblScope><biblScope unit="page" to="1125">1125</biblScope></imprint><idno type="ISSN">0035-9203</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0035-9203</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Albendazole</term><term>Diethylcarbamazine</term><term>Lymphatic filariasis</term><term>Macrofilaricidal effect</term><term>Microfilaria</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract">Although diethylcarbamazine (DEC) and albendazole are recommended to interrupt transmission of Wuchereria bancrofti, little is known about the macrofilaricidal effect of this drug combination. Forty-seven men with W. bancrofti infection were randomly assigned to receive a single dose of either DEC alone (6 mg/kg) (n = 25) or a combination of DEC (6 mg/kg) and albendazole (400 mg) (n = 22). Physical examinations for scrotal nodules (resulting from worm death) and ultrasound examinations (to detect living adult worms) were performed before treatment and 7, 14, 30, 45, 60, 90, 180, 270 and 360 days after treatment. Blood was examined for microfilariae before and 30 days and 360 days after treatment. Seven days post treatment, intrascrotal nodules were detected at the site of 21 (46.7%) adult worm nests in men who received DEC alone compared with 2 (6.1%) sites in men who received DEC and albendazole (P = 0.002). One year after treatment, 10 (22.2%) original adult worm nests remained detectable by ultrasound among men who received DEC alone compared with 18/32 (56.3%) nests among men who received both drugs (P = 0.016). Microfilaraemia prevalence and density decreased to a similar extent in both groups. Addition of albendazole appeared to decrease the macrofilaricidal effect of DEC against W. bancrofti, with no detectable enhancement in microfilarial suppression.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Gerusa Dreyer</name><affiliations><json:string>NEPAF, Hospital das Clínicas, Universidade Federal de Pernambuco, Av. 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Forty-seven men with W. bancrofti infection were randomly assigned to receive a single dose of either DEC alone (6 mg/kg) (n = 25) or a combination of DEC (6 mg/kg) and albendazole (400 mg) (n = 22). Physical examinations for scrotal nodules (resulting from worm death) and ultrasound examinations (to detect living adult worms) were performed before treatment and 7, 14, 30, 45, 60, 90, 180, 270 and 360 days after treatment. Blood was examined for microfilariae before and 30 days and 360 days after treatment. Seven days post treatment, intrascrotal nodules were detected at the site of 21 (46.7%) adult worm nests in men who received DEC alone compared with 2 (6.1%) sites in men who received DEC and albendazole (P = 0.002). One year after treatment, 10 (22.2%) original adult worm nests remained detectable by ultrasound among men who received DEC alone compared with 18/32 (56.3%) nests among men who received both drugs (P = 0.016). Microfilaraemia prevalence and density decreased to a similar extent in both groups. 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Prof. Moraes Rego s/n, Cidade Universitária, CEP 50740-900, Recife PE, Brazil</affiliation><affiliation>Departmento de Cirurgia, Hospital das Clínicas, Universidade Federal de Pernambuco, Recife PE, Brazil</affiliation></author><idno type="istex">08BDB13FA4F7E3873CC5F56ADC64278EFCC04AA2</idno><idno type="DOI">10.1016/j.trstmh.2006.04.006</idno></analytic><monogr><title level="j">Transactions of The Royal Society of Tropical Medicine and Hygiene</title><title level="j" type="abbrev">Trans R Soc Trop Med Hyg</title><idno type="pISSN">0035-9203</idno><idno type="eISSN">1878-3503</idno><idno type="PublisherID">trstmh</idno><idno type="PublisherID-hwp">trstmh</idno><imprint><publisher>Royal Society of Tropical Medicine and Hygiene</publisher><date type="published" when="2006-12"></date><biblScope unit="volume">100</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="1118">1118</biblScope><biblScope unit="page" to="1125">1125</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2006</date></creation><abstract><p>Although diethylcarbamazine (DEC) and albendazole are recommended to interrupt transmission of Wuchereria bancrofti, little is known about the macrofilaricidal effect of this drug combination. Forty-seven men with W. bancrofti infection were randomly assigned to receive a single dose of either DEC alone (6 mg/kg) (n = 25) or a combination of DEC (6 mg/kg) and albendazole (400 mg) (n = 22). Physical examinations for scrotal nodules (resulting from worm death) and ultrasound examinations (to detect living adult worms) were performed before treatment and 7, 14, 30, 45, 60, 90, 180, 270 and 360 days after treatment. Blood was examined for microfilariae before and 30 days and 360 days after treatment. Seven days post treatment, intrascrotal nodules were detected at the site of 21 (46.7%) adult worm nests in men who received DEC alone compared with 2 (6.1%) sites in men who received DEC and albendazole (P = 0.002). One year after treatment, 10 (22.2%) original adult worm nests remained detectable by ultrasound among men who received DEC alone compared with 18/32 (56.3%) nests among men who received both drugs (P = 0.016). Microfilaraemia prevalence and density decreased to a similar extent in both groups. Addition of albendazole appeared to decrease the macrofilaricidal effect of DEC against W. bancrofti, with no detectable enhancement in microfilarial suppression.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Lymphatic filariasis</term></item><item><term>Albendazole</term></item><item><term>Diethylcarbamazine</term></item><item><term>Macrofilaricidal effect</term></item><item><term>Microfilaria</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2006-12">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/08BDB13FA4F7E3873CC5F56ADC64278EFCC04AA2/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup, element #text not found" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article">
<front>
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<journal-id journal-id-type="hwp">trstmh</journal-id>
<journal-id journal-id-type="publisher-id">trstmh</journal-id>
<journal-title>Transactions of The Royal Society of Tropical Medicine and Hygiene</journal-title>
<abbrev-journal-title>Trans R Soc Trop Med Hyg</abbrev-journal-title>
<issn pub-type="ppub">0035-9203</issn>
<issn pub-type="epub">1878-3503</issn>
<publisher>
<publisher-name>Royal Society of Tropical Medicine and Hygiene</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.1016/j.trstmh.2006.04.006</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Articles</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Efficacy of co-administered diethylcarbamazine and albendazole against adult <italic>Wuchereria bancrofti</italic></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name><surname>Dreyer</surname><given-names>Gerusa</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff2"><sup>b</sup></xref><xref ref-type="corresp" rid="cor1"><sup>⁎</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Addiss</surname><given-names>David</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Williamson</surname><given-names>John</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Norões</surname><given-names>Joaquim</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff4"><sup>d</sup></xref>
</contrib>
<aff id="aff1">
<label>a</label>NEPAF, Hospital das Clínicas, Universidade Federal de Pernambuco, Av. Prof. Moraes Rego s/n, Cidade Universitária, CEP 50740-900, Recife PE, Brazil</aff>
<aff id="aff2">
<label>b</label>Centro do Pesquisas Aggeu Magalhaes, FIOCRUZ, Recife PE, Brazil</aff>
<aff id="aff3">
<label>c</label>Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA</aff>
<aff id="aff4">
<label>d</label>Departmento de Cirurgia, Hospital das Clínicas, Universidade Federal de Pernambuco, Recife PE, Brazil</aff>
</contrib-group>
<author-notes>
<corresp id="cor1">
<label>⁎</label>Corresponding author. Tel.: +55 81 3426 4348; fax: +55 81 3426 4348. <italic>E-mail address</italic>: <email>dreyer-g@uol.com.br</email> (G. Dreyer).</corresp>
</author-notes>
<pub-date pub-type="ppub">
<month>12</month>
<year>2006</year>
</pub-date>
<volume>100</volume>
<issue>12</issue>
<fpage>1118</fpage>
<lpage>1125</lpage>
<history>
<date date-type="received">
<day>1</day>
<month>9</month>
<year>2005</year></date>
<date date-type="rev-recd">
<day>4</day>
<month>4</month>
<year>2006</year></date>
<date date-type="accepted">
<day>4</day>
<month>4</month>
<year>2006</year></date>
</history>
<permissions>
<copyright-year>2006</copyright-year>
<copyright-holder>Royal Society of Tropical Medicine and Hygiene</copyright-holder>
</permissions>
<abstract>
<title>Summary</title>
<p>Although diethylcarbamazine (DEC) and albendazole are recommended to interrupt transmission of <italic>Wuchereria bancrofti</italic>, little is known about the macrofilaricidal effect of this drug combination. Forty-seven men with <italic>W. bancrofti</italic> infection were randomly assigned to receive a single dose of either DEC alone (6 mg/kg) (<italic>n</italic> = 25) or a combination of DEC (6 mg/kg) and albendazole (400 mg) (<italic>n</italic> = 22). Physical examinations for scrotal nodules (resulting from worm death) and ultrasound examinations (to detect living adult worms) were performed before treatment and 7, 14, 30, 45, 60, 90, 180, 270 and 360 days after treatment. Blood was examined for microfilariae before and 30 days and 360 days after treatment. Seven days post treatment, intrascrotal nodules were detected at the site of 21 (46.7%) adult worm nests in men who received DEC alone compared with 2 (6.1%) sites in men who received DEC and albendazole (<italic>P</italic> = 0.002). One year after treatment, 10 (22.2%) original adult worm nests remained detectable by ultrasound among men who received DEC alone compared with 18/32 (56.3%) nests among men who received both drugs (<italic>P</italic> = 0.016). Microfilaraemia prevalence and density decreased to a similar extent in both groups. Addition of albendazole appeared to decrease the macrofilaricidal effect of DEC against <italic>W. bancrofti</italic>, with no detectable enhancement in microfilarial suppression.</p>
</abstract>
<kwd-group xml:lang="en">
<title>Keywords</title>
<kwd>Lymphatic filariasis</kwd>
<kwd><italic>Wuchereria bancrofti</italic></kwd>
<kwd>Albendazole</kwd>
<kwd>Diethylcarbamazine</kwd>
<kwd>Macrofilaricidal effect</kwd>
<kwd>Microfilaria</kwd>
</kwd-group>
</article-meta>
</front>
<body>
<sec>
<label>1</label>
<title>Introduction</title>
<p>In 1998, the WHO announced the Global Program to Eliminate Lymphatic Filariasis, with the goal of eliminating lymphatic filariasis as a public health problem. In filariasis-endemic areas outside sub-Saharan Africa, the strategy most commonly used to interrupt transmission of the parasite is annual single-dose mass treatment with diethylcarbamazine (DEC) 6 mg/kg and albendazole 400 mg. This two-drug combination has been shown in some (<xref ref-type="bibr" rid="bib21">Fox et al., 2005</xref>; <xref ref-type="bibr" rid="bib23">Gyapong et al., 2005</xref>) but not all (<xref ref-type="bibr" rid="bib28">Kshirsagar et al., 2004</xref>; <xref ref-type="bibr" rid="bib35">Pani et al., 2002</xref>) studies to suppress microfilarial density in the blood of infected persons more profoundly than DEC alone. Co-administration of albendazole and DEC also provides a broad public health benefit owing to the action of albendazole against a range of intestinal helminths (<xref ref-type="bibr" rid="bib4">Beau de Rochars et al., 2004</xref>; <xref ref-type="bibr" rid="bib29">Mani et al., 2004</xref>; <xref ref-type="bibr" rid="bib34">Ottesen et al., 2000</xref>).</p>
<p>In addition to its microfilaricidal effect, DEC kills a certain percentage of adult <italic>Wuchereria bancrofti</italic> (<xref ref-type="bibr" rid="bib7">Dreyer et al., 1995a</xref>; <xref ref-type="bibr" rid="bib31">Norões et al., 1997</xref>). Macrofilaricidal activity can reduce the number of rounds of mass treatment needed to interrupt parasite transmission and remove the biological stimulus for progressive lymphangiectasia (<xref ref-type="bibr" rid="bib15">Dreyer et al., 2002</xref>). The extent to which the addition of albendazole enhances the macrofilaricidal effect of single-dose DEC is unknown. Several studies have reported that the drug combination decreases circulating filarial antigen levels or the number of adult worm nests detectable by ultrasound (<xref ref-type="bibr" rid="bib17">El Setouhy et al., 2004</xref>; <xref ref-type="bibr" rid="bib21">Fox et al., 2005</xref>; <xref ref-type="bibr" rid="bib24">Hussein et al., 2004</xref>; <xref ref-type="bibr" rid="bib25">Ismail et al., 1998</xref>, <xref ref-type="bibr" rid="bib26">2001</xref>; <xref ref-type="bibr" rid="bib28">Kshirsagar et al., 2004</xref>; <xref ref-type="bibr" rid="bib35">Pani et al., 2002</xref>). However, only three of these studies included DEC-only controls, and in these studies no significant differences were found between the two treatment groups. Furthermore, no previous studies have followed subjects both with physical and ultrasound examinations to monitor the adult worms.</p>
<p>Tender, palpable inflammatory nodules develop at the site of dead or dying adult <italic>W. bancrofti</italic> (<xref ref-type="bibr" rid="bib13">Dreyer et al., 1999a</xref>; <xref ref-type="bibr" rid="bib33">Ottesen, 1985</xref>). In adult men, they are recognised most commonly in the intrascrotal lymphatic vessels, the ‘preferred’ site of <italic>W. bancrofti</italic> in men (<xref ref-type="bibr" rid="bib7">Dreyer et al., 1995a</xref>; <xref ref-type="bibr" rid="bib19">Figueredo-Silva et al., 1996</xref>; <xref ref-type="bibr" rid="bib31">Norões et al., 1997</xref>, <xref ref-type="bibr" rid="bib32">2003</xref>; <xref ref-type="bibr" rid="bib39">Reddy et al., 2004</xref>). The sensitivity with which nodule palpation detects death of all adult <italic>W. bancrofti</italic> is unknown, as is the degree to which this might vary by examiner and in different settings. However, the specificity of this finding in our setting, based on hundreds of biopsies, appears to be 100% (<xref ref-type="bibr" rid="bib6">Dreyer et al., 1994</xref>, <xref ref-type="bibr" rid="bib8">1995b</xref>, <xref ref-type="bibr" rid="bib11">1998a</xref>, <xref ref-type="bibr" rid="bib14">1999b</xref>; <xref ref-type="bibr" rid="bib19">Figueredo-Silva et al., 1996</xref>, <xref ref-type="bibr" rid="bib20">2002</xref>; <xref ref-type="bibr" rid="bib31">Norões et al., 1997</xref>, <xref ref-type="bibr" rid="bib32">2003</xref>).</p>
<p>The most direct indicator of living <italic>W. bancrofti</italic> is the ‘filaria dance sign’ (FDS) (<xref ref-type="bibr" rid="bib10">Dreyer et al., 1996b</xref>; <xref ref-type="bibr" rid="bib30">Norões et al., 1996</xref>, <xref ref-type="bibr" rid="bib31">1997</xref>, <xref ref-type="bibr" rid="bib32">2003</xref>), the characteristic aleatoric movement of living adult worms that is seen on ultrasound (<xref ref-type="bibr" rid="bib1">Amaral et al., 1994</xref>). The sensitivity of this finding for the presence of living intrascrotal worms depends on, among other factors, lymphatic vessel diameter (<xref ref-type="bibr" rid="bib12">Dreyer et al., 1998b</xref>); its specificity in our hands, based on more than 100 patients who subsequently had the worms surgically removed, is 100% (<xref ref-type="bibr" rid="bib1">Amaral et al., 1994</xref>, <xref ref-type="bibr" rid="bib2">1995</xref>; <xref ref-type="bibr" rid="bib3">Araújo et al., 1995</xref>; <xref ref-type="bibr" rid="bib11">Dreyer et al., 1998a</xref>; <xref ref-type="bibr" rid="bib31">Norões et al., 1997</xref>; <xref ref-type="bibr" rid="bib36">Peixoto, 2005</xref>; <xref ref-type="bibr" rid="bib37">Peixoto and Figueredo-Silva, 2001</xref>; <xref ref-type="bibr" rid="bib38">Peixoto et al., 1999</xref>; <xref ref-type="bibr" rid="bib40">Rocha et al., 1996</xref>). These two clinical tools (physical and ultrasound examination) are best used together to monitor the macrofilaricidal effectiveness of antifilarial drugs (<xref ref-type="bibr" rid="bib7">Dreyer et al., 1995a</xref>, <xref ref-type="bibr" rid="bib8">1995b</xref>, <xref ref-type="bibr" rid="bib9">1996a</xref>, <xref ref-type="bibr" rid="bib11">1998a</xref>, <xref ref-type="bibr" rid="bib14">1999b</xref>; <xref ref-type="bibr" rid="bib19">Figueredo-Silva et al., 1996</xref>; <xref ref-type="bibr" rid="bib31">Norões et al., 1997</xref>, <xref ref-type="bibr" rid="bib32">2003</xref>). Following treatment, three outcomes are possible for each living adult worm nest. If the drugs kill all adult worms in the nest, a tender nodule develops and the FDS ceases (‘drug sensitive’). If the adult worm is unaffected, no nodule is detected and the FDS persists (‘non-sensitive’). A mixed reaction is also possible, in which some but not all adult worms are killed; in this case a nodule develops but the FDS persists at the site of the nodule (<xref ref-type="bibr" rid="bib16">Dreyer et al., 2005</xref>; <xref ref-type="bibr" rid="bib20">Figueredo-Silva et al., 2002</xref>; <xref ref-type="bibr" rid="bib31">Norões et al., 1997</xref>).</p>
<p>We used repeated physical and ultrasound examinations to compare the macrofilaricidal effectiveness of DEC alone with that of DEC and albendazole. We also examined blood for microfilariae before and after treatment.</p>
</sec>
<sec sec-type="methods">
<label>2</label>
<title>Methods</title>
<p>The study was conducted in the outpatient clinic of NEPAF, Hospital das Clínicas, Federal University of Pernambuco, Recife, Brazil. The study protocol was approved by the Ethics Committee of Hospital das Clínicas. After obtaining informed consent, adult males seeking treatment for Bancroftian filariasis underwent physical and ultrasound examinations of the scrotal area on two separate occasions to confirm the absence of intrascrotal nodules and the reproducibility of the FDS. Physical and ultrasound examinations of the lymphatic vessels and lymph nodes elsewhere in the body were also performed. Ultrasound examinations were performed using a portable ALOKA SSD-500 (Japan) or a portable Pie Medical 200 (The Netherlands) ultrasound machine, both equipped with a 7.5 mHz probe. One millilitre samples of blood were collected from each subject at night and filtered through a 3 μm Nuclepore filter (Nuclepore Corporation, Pleasanton, CA, USA). The filter was placed on a slide, stained and examined for <italic>W. bancrofti</italic> microfilariae. Men were eligible for this study if they: (1) were at least 18 years of age; (2) had reproducibility of the FDS confirmed by two independent investigators on three separate occasions (several days apart) before treatment; (3) had no hydrocele or genital lymphoedema; (4) had never been treated for filarial infection with DEC or ivermectin; (5) received no anthelminthic drugs during the follow-up period; and (6) adhered to the follow-up schedule for physical and ultrasound examinations.</p>
<p>The men were randomly assigned to a treatment group and were treated under direct observation with either a single 6 mg/kg dose of DEC alone (Farmanguinhos, FIOCRUZ, Recife, Brazil) or a combined single dose of DEC (6 mg/kg) and albendazole (400 mg) (Zentel<sup>®</sup>; GlaxoSmithKline Brasil Ltda., Rio de Janeiro, Brazil). The physician performing the physical examinations (J.N.) was unaware of the subject's treatment status or ultrasound findings. Two sonographers independently performed ultrasound examinations; one of these examiners remained blinded both to treatment status and physical examination results throughout the study.</p>
<p>Physical and ultrasound examinations were performed 7, 14, 30, 45, 60, 90, 180, 270 and 360 days after antifilarial drug treatment. One millilitre samples of nocturnal blood were obtained for filtration and determination of microfilarial density 30 days and 360 days after treatment.</p>
<p>As is routine practice at NEPAF, all patients in the study received information about lymphatic filariasis and its transmission as well as a bed net for their own use. The nets were not impregnated with insecticide. During the year following treatment, the bed nets were checked every 4 months and replaced if necessary.</p>
<sec>
<label>2.1</label>
<title>Statistical methods</title>
<p>Analyses used either individual men or adult worm nests as the unit of analysis. Differences in proportions were tested using Fisher's exact test. Differences in the distribution of continuous variables were tested with the non-parametric Wilcoxon rank-sum test. To control for potential confounders (e.g. patient age, number of nests), to address the fact that multiple nests within a single man may not be biologically independent and to assess the presence of interaction among variables, generalised estimating equations (PROC GENMOD, SAS release 9.1; SAS Institute, Cary, NC, USA) were used. Survival curves were plotted for adult worm nests for both groups, assuming that the data were interval-censored (<xref ref-type="bibr" rid="bib18">Fay, 2005</xref>; <xref ref-type="bibr" rid="bib42">Turnbull, 1976</xref>).</p>
</sec>
<sec id="sec1">
<label>2.2</label>
<title>Definition of terms (<xref ref-type="bibr" rid="bib31">Norões et al., 1997</xref>)</title>
<p>A nodule was defined as a palpable, cord-like, spherical or egg-shaped mass in an intrascrotal lymphatic vessel, which varied from hard to rubbery in consistency. A sensitive reaction to antifilarial drugs was defined as disappearance of the FDS and the detection of a scrotal nodule by palpation. A non-sensitive reaction was defined as a persistent FDS in the absence of a palpable nodule at the site. A mixed reaction, indicating death of at least one but not all adult worms, was defined as a persistent FDS in the presence of a new palpable nodule.</p>
</sec>
</sec>
<sec>
<label>3</label>
<title>Results</title>
<sec>
<label>3.1</label>
<title>Pre-treatment observations</title>
<p>A total of 47 men participated in the study: 25 received a single 6 mg/kg dose of DEC and 22 received both DEC and albendazole. Men who were treated with DEC alone were significantly younger (mean age, 21.5 years) than those who received both drugs (mean, 29.4 years). Before treatment, a total of 78 adult worm nests were detected by ultrasound (mean, 1.7 nests per person; range, 1–5). The mean number of adult worm nests did not differ significantly between the two treatment groups: 1.8 (total, 45 nests) for men who received DEC and 1.5 (total, 33 nests) for those who were treated with both drugs (<xref ref-type="fig" rid="tbl1">Table 1</xref>
<fig id="tbl1">
<label>Table 1</label>
<caption>
<p>Characteristics and treatment-related outcomes for 47 men with <italic>Wuchereria bancrofti</italic> infection who received a single 6 mg/kg dose of diethylcarbamazine (DEC) (<italic>n</italic> = 25) or a combined single dose of DEC (6 mg/kg) and albendazole (400 mg) (<italic>n</italic> = 22), Recife, Brazil</p>
</caption>
<graphic mimetype="image" xlink:href="100-12-1118-tbl001.tif"></graphic>
</fig>). The geometric mean microfilarial density did not differ significantly between the two groups (130 and 56 microfilariae per ml of blood for those receiving DEC alone and the two-drug combination, respectively). None of the patients had the FDS detectable outside the intrascrotal lymphatics.</p>
</sec>
<sec>
<label>3.2</label>
<title>Macrofilaricidal effect within 7 days after treatment</title>
<p>Seven days post treatment, when local adverse reactions associated with drug-related adult worm death are commonly recognised (<xref ref-type="bibr" rid="bib7">Dreyer et al., 1995a</xref>; <xref ref-type="bibr" rid="bib32">Norões et al., 2003</xref>), intrascrotal nodules were detected at the site of 21 (46.7%) adult worm nests in men who received DEC alone compared with 2 (6.1%) in men who received both DEC and albendazole (<italic>P</italic> = 0.002). None of the patients had post-treatment adenitis or nodules detected outside the scrotal area. Of the 23 intrascrotal nodules, 9 were completely drug-sensitive, i.e. no FDS was detectable at the site of the nodule for the duration of the study, indicating the absence of living adult <italic>W. bancroft</italic>i within the nest (<xref ref-type="fig" rid="fig1">Figure 1</xref>
<fig id="fig1" position="float">
<label>Figure 1</label>
<caption>
<p>Outcome of nests of living adult <italic>Wuchereria bancrofti</italic> following single-dose treatment with diethylcarbamazine (DEC) alone (45 nests in 25 men) or co-administered DEC and albendazole (ALB) (33 nests in 22 men), Recife, Brazil. Definitions of sensitive, non-sensitive and mixed are provided in Section <xref ref-type="sec" rid="sec1">2.2</xref>. New adult worm nests and scrotal nodules, first detected in new sites 30–360 days after treatment, are indicated in the last row of the figure.</p>
</caption>
<graphic mimetype="image" xlink:href="100-12-1118-fig001.jpg"></graphic>
</fig>). Seven of these nests that contained only drug-sensitive worms were found in men who received DEC alone and two were in those who received both drugs (<italic>P</italic> = NS). The remaining 14 nodules, all in men who received DEC alone, exhibited mixed reactions, i.e. some adult worm movement within the nest (i.e. nodule) was still detectable by ultrasound. In a multivariate analysis that controlled for patient age and number of nests, only the drug was significantly associated with nodule formation (odds ratio for DEC alone = 20.7, 95% CI 2.1–209.3).</p>
<p>One man who received both DEC and albendazole and whose single adult worm nest remained unchanged elected to undergo surgery 90 days post treatment to remove the adult worms (i.e. a surgical cure). At surgery, three living adult <italic>W. bancrofti</italic> were removed from the dilated intrascrotal lymphatic vessels, two females and one male. This man was excluded from all analyses of data collected >7 days post treatment.</p>
</sec>
<sec>
<label>3.3</label>
<title>Nodules 14–360 days after treatment</title>
<p>Seven days after treatment, the FDS remained detectable in 38 nests in men who had received DEC and in 30 nests in men who received both drugs (<xref ref-type="fig" rid="fig1">Figure 1</xref>; <xref ref-type="fig" rid="tbl1">Table 1</xref>). Physical and ultrasound examinations during the remainder of the study revealed new nodules (indicating adult worm death) at the site of 29 (76.3%) of these nests in men who received DEC alone and 13 (43.3%) nests in men who received both drugs (<italic>P</italic> = 0.024). These nodules were first detected 14–360 days after treatment (median, 60 days; mean, 104 days). The nodules, 23 on the left side and 19 on the right, included five mixed reaction nodules, two of which had persistent FDS for the remainder of the study and three of which had no detectable FDS on any subsequent ultrasound examinations (<xref ref-type="fig" rid="fig1">Figure 1</xref>). Frequency of nodule formation during this period was not associated with the pre-treatment number of adult worm nests (data not shown).</p>
<p>Adult worm nests that had mixed reactions detected on Day 7 were no more likely than non-sensitive nests to develop new nodules 14–360 days after treatment. Of the 14 nests that had mixed reactions on Day 7, 10 subsequently developed nodules (1 of which was mixed and the FDS persisted until the end of the study). Thus, in 5 (35.7%) of these 14 nests, the FDS persisted throughout the study, compared with 23 (42.6%) of 54 nests that were not sensitive to antifilarial drugs within 7 days after treatment (<italic>P</italic> = 0.76).</p>
</sec>
<sec>
<label>3.4</label>
<title>Ultrasound 1 year after treatment</title>
<p>The two sonographers agreed on ultrasound findings for all study subjects. At the end of the study, 10 (22.2%) of 45 original adult worm nests remained detectable by ultrasound among men who received DEC alone compared with 18 (56.3%) of 32 nests among men who received both DEC and albendazole (<italic>P</italic> = 0.016). The increased rate of FDS disappearance among men who received DEC alone appeared to be limited to the first 3 months after treatment (<xref ref-type="fig" rid="fig2">Figure 2</xref>
<fig id="fig2" position="float">
<label>Figure 2</label>
<caption>
<p>Kaplan–Meier plot of the proportion of adult worm nests that continued to have detectable filaria dance signs (survival), by treatment group: diethylcarbamazine (DEC) alone (solid line) and DEC–albendazole combination (dashed line).</p>
</caption>
<graphic mimetype="image" xlink:href="100-12-1118-fig002.jpg"></graphic>
</fig>). In a multivariate analysis that controlled for patient age and number of nests, cessation of the FDS was significantly associated with having received DEC alone (<italic>P</italic> = 0.03) and having fewer adult worm nests (<italic>P</italic> = 0.02). However, an interaction was observed between the drug regimen and the number of nests (<italic>P</italic> = 0.045). Among men who received DEC alone, cessation of the FDS (in 77.8% of nests) was not associated with the number of adult worm nests per patient. In contrast, among men who received both drugs, the FDS disappeared in 10 (76.9%) of 13 nests in men who had only 1 nest and in 4 (21.1%) of 19 nests in men who had 2 to 4 adult worm nests (<italic>P</italic> = 0.006, χ<sup>2</sup>).</p>
</sec>
<sec>
<label>3.5</label>
<title>Incidence of new nests and nodules</title>
<p>During this 12-month study, new nodules and adult worm nests appeared in intrascrotal locations where the FDS had not previously been detected. One man had a new living adult worm nest that was first detected by ultrasound 180 days after treatment. This man, who had been treated with both DEC and albendazole, had four other adult worm nests that had been detected by ultrasound before treatment. The FDS in the new nest persisted for the duration of the study.</p>
<p>In addition, 30–360 days after treatment (median, 270 days), eight intrascrotal nodules were detected in sites where no FDS had previously been detected. This was observed in four men in each treatment group. No FDS was ever detected at the site of these nodules. These findings were consistent with death of all adult worms in nests that had been smaller than the limit of detection by ultrasound (approximately 1 mm) (<xref ref-type="bibr" rid="bib30">Norões et al., 1996</xref>).</p>
</sec>
<sec>
<label>3.6</label>
<title>Microfilaricidal effect</title>
<p>Microfilaraemia prevalence and density decreased significantly in both groups following treatment (<xref ref-type="fig" rid="tbl1">Table 1</xref>), but no significant differences were observed between groups, either at 30 days or 360 days after treatment.</p>
</sec>
</sec>
<sec>
<label>4</label>
<title>Discussion</title>
<p>The announcement by SmithKline Beecham in 1998 that it would donate an estimated five billion doses of albendazole to the WHO for lymphatic filariasis highlighted the global importance of this neglected disease and helped to mobilise additional resources for the fledgling campaign to eliminate it. One of the primary benefits of co-administering albendazole with DEC is the additive effect that albendazole has against a broader range of intestinal helminths (<xref ref-type="bibr" rid="bib4">Beau de Rochars et al., 2004</xref>; <xref ref-type="bibr" rid="bib29">Mani et al., 2004</xref>; <xref ref-type="bibr" rid="bib34">Ottesen et al., 2000</xref>). Another benefit, enhanced microfilarial suppression, has been reported in some but not all studies (<xref ref-type="bibr" rid="bib21">Fox et al., 2005</xref>; <xref ref-type="bibr" rid="bib23">Gyapong et al., 2005</xref>; <xref ref-type="bibr" rid="bib35">Pani et al., 2002</xref>; <xref ref-type="bibr" rid="bib41">Tisch et al., 2005</xref>). We found no difference in short-term microfilarial clearance or longer-term microfilarial suppression, measured at 1 month and 12 months after treatment, respectively, between men who received DEC alone and those who received both DEC and albendazole.</p>
<p>The major focus of the current study was the effect of co-administered DEC and albendazole against the adult worm. Most previous studies have assessed the macrofilaricidal effect of this drug combination by measuring circulating filarial antigen levels. In these studies, combined DEC and albendazole reduced antigen prevalence by 5–77% and antigen density by 27–90% (<xref ref-type="bibr" rid="bib17">El Setouhy et al., 2004</xref>; <xref ref-type="bibr" rid="bib21">Fox et al., 2005</xref>; <xref ref-type="bibr" rid="bib24">Hussein et al., 2004</xref>; <xref ref-type="bibr" rid="bib25">Ismail et al., 1998</xref>, <xref ref-type="bibr" rid="bib26">2001</xref>; <xref ref-type="bibr" rid="bib28">Kshirsagar et al., 2004</xref>; <xref ref-type="bibr" rid="bib35">Pani et al., 2002</xref>). However, none of the studies that included a DEC-only control group reported significant differences in post-treatment antigen prevalence or density between the two treatment groups (<xref ref-type="bibr" rid="bib21">Fox et al., 2005</xref>; <xref ref-type="bibr" rid="bib28">Kshirsagar et al., 2004</xref>; <xref ref-type="bibr" rid="bib35">Pani et al., 2002</xref>). Unfortunately, stored serum specimens from the current study were destroyed during an electrical power failure. Thus, testing for antigenaemia, which would have allowed a direct comparison between antigenaemia, physical examination for nodules and ultrasound, was not possible.</p>
<p>Our results, which were based on physical and ultrasound examinations, suggest that a single co-administered dose of albendazole may actually inhibit the macrofilaricidal effect of DEC. Within 7 days after treatment, almost one-half of adult worm nests in men who received DEC alone developed inflammatory nodules compared with only 6% of nests in men who were treated with both drugs. Furthermore, 1 year after treatment, persistence of the FDS was more frequently observed in men who received both DEC and albendazole. This apparent ‘inhibitory’ effect of co-administered albendazole on the macrofilaricidal efficacy of DEC was unexpected, particularly since albendazole in repeated high doses has been reported to kill <italic>W. bancrofti</italic> (<xref ref-type="bibr" rid="bib27">Jayakody et al., 1993</xref>). The mechanism of action of DEC is poorly understood and sensitivity of adult <italic>W. bancrofti</italic> to the drug is variable, even within the same patient (<xref ref-type="bibr" rid="bib31">Norões et al., 1997</xref>). It appears to act by stimulating the immune system rather than by any direct effect on the worms themselves. Thus, it is not inconceivable that simultaneous administration of another drug might interfere with this mechanism, perhaps by interfering with antigenic sites on the worm that are targeted by a DEC-triggered immunological response. A similar decrease in macrofilaricidal efficacy has been reported when ivermectin was co-administered with DEC (<xref ref-type="bibr" rid="bib11">Dreyer et al., 1998a</xref>). Available evidence indicates no effect of co-administered albendazole on blood levels of DEC (<xref ref-type="bibr" rid="bib28">Kshirsagar et al., 2004</xref>).</p>
<p>Only one previous study used ultrasound to monitor the macrofilaricidal efficacy of combined single-dose DEC and albendazole. Of 15 persons, 12 (80%) had complete clearance of the FDS 12 months after treatment (<xref ref-type="bibr" rid="bib17">El Setouhy et al., 2004</xref>; <xref ref-type="bibr" rid="bib24">Hussein et al., 2004</xref>), similar to the 78% figure among patients in our study who received only DEC. Unfortunately, this previous study did not include a DEC-only treatment group and sequential physical examinations for intrascrotal nodules were not performed.</p>
<p>The macrofilaricidal effect of DEC, as determined by development of scrotal nodules, is usually observed within 7 days after treatment (<xref ref-type="bibr" rid="bib7">Dreyer et al., 1995a</xref>; <xref ref-type="bibr" rid="bib32">Norões et al., 2003</xref>). In the current study, cessation of the FDS and detection of new nodules continued beyond this point and, until 3 months after treatment, were observed more frequently in men who received DEC alone than in men who received both drugs. This observation suggests the possibility of a delayed effect of DEC alone against the adult worm. Interestingly, a recent study of <italic>Brugia pahangi</italic> in jirds showed no macrofilaricidal effect of DEC until 8 weeks after treatment (<xref ref-type="bibr" rid="bib22">Fujimaki et al., 2004</xref>). In a previous study by our group, the FDS became non-detectable in 51% of adult worm nests 3 months after treatment with ≥6 mg/kg of DEC alone (<xref ref-type="bibr" rid="bib31">Norões et al., 1997</xref>) compared with 78% (1 year after treatment) in the current study. The longer duration of post-treatment follow-up in the current study may have contributed to the observed differences between the two studies.</p>
<p>We have previously reported that the background rates of natural adult worm death and nodule formation vary among individuals (<xref ref-type="bibr" rid="bib32">Norões et al., 2003</xref>), which appears to depend in part on the intensity of transmission. We cannot rule out differences in exposure to <italic>W. bancrofti</italic> between the two treatment groups. However, indirect measures of transmission intensity were similar for both groups: before treatment, microfilarial density and number of adult worm nests were similar, and the number of new nests of living adult worms detected by ultrasound during the 12 months after treatment was identical. Furthermore, all men were provided bed nets and encouraged to sleep under them.</p>
<p>The degree to which adding albendazole to single-dose DEC enhances microfilarial suppression has varied among studies, although the effect appears to be statistically significant primarily within the first 6 months (<xref ref-type="bibr" rid="bib5">Critchley et al., 2005</xref>; <xref ref-type="bibr" rid="bib23">Gyapong et al., 2005</xref>; <xref ref-type="bibr" rid="bib41">Tisch et al., 2005</xref>). In the current study, post-treatment microfilaraemia was similar for the two treatment groups, although macrofilaricidal efficacy appeared to differ. Such a discrepancy is not surprising. The number of adult worm nests is generally thought to correlate with microfilarial density (<xref ref-type="bibr" rid="bib12">Dreyer et al., 1998b</xref>; <xref ref-type="bibr" rid="bib30">Norões et al., 1996</xref>), however the factors that affect microfilaria production, release and longevity, even in the absence of drug treatment, are poorly understood.</p>
<p>This study has several limitations. Because only men were studied, it is unknown whether similar results would be found for women and children. The number of study subjects was relatively small and the men came from only one filariasis-endemic area. Therefore, we cannot generalise these findings to other endemic areas. The study subjects were followed for only 1 year and only one dose of treatment was given. Whether co-administered albendazole would have a similar effect during subsequent treatment rounds is unknown. This study involved individual treatment rather than mass treatment. Thus, we did not evaluate the effect of the drugs on parasite transmission.</p>
<p>The results of this study do not indicate that co-administration of albendazole with DEC would be less effective than DEC alone in interrupting transmission. At the programme level, many factors other than macrofilaricidal efficacy, such as the depth and duration of microfilarial suppression, the fecundity of the remaining adult worms, the mosquito vector species and the potential for greater acceptance and higher coverage of mass drug treatment resulting from drug effectiveness against intestinal worms, will likely play important roles.</p>
<p>None the less, this study highlights the complexity of <italic>W. bancrofti</italic> biology and ecology. Surprisingly little is known about the biology of the parasite within the human host, the mechanism of action of antifilarial drugs or the population dynamics of the parasite under varying ecological conditions and transmission intensities, including those of mass drug treatment with antifilarial drug combinations. Improved understanding of these issues is likely to be critical for successful global elimination of <italic>W. bancrofti</italic>. Finally, all current methods for assessing adult worm viability and mortality, including physical examination for nodules, ultrasound and antigen testing, have their limitations. A standardised prospective approach incorporating all three methods should be adopted for future studies of macrofilaricidal drug efficacy.</p>
</sec>
<sec>
<title>Conflicts of interest statement</title>
<p>The authors have no conflicts of interest concerning the work reported in this paper.</p>
</sec>
</body>
<back>
<ack>
<title>Acknowledgements</title>
<p>This study was supported by Amaury Coutinho Non-Governmental Organization, Recife, Brazil. The authors thank the patients who participated in the study.</p>
</ack>
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</article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Efficacy of co-administered diethylcarbamazine and albendazole against adult Wuchereria bancrofti</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Efficacy of co-administered diethylcarbamazine and albendazole against adult Wuchereria bancrofti</title></titleInfo><name type="personal" displayLabel="corresp"><namePart type="given">Gerusa</namePart><namePart type="family">Dreyer</namePart><affiliation>NEPAF, Hospital das Clínicas, Universidade Federal de Pernambuco, Av. Prof. Moraes Rego s/n, Cidade Universitária, CEP 50740-900, Recife PE, Brazil</affiliation><affiliation>Centro do Pesquisas Aggeu Magalhaes, FIOCRUZ, Recife PE, Brazil</affiliation><affiliation>E-mail: dreyer-g@uol.com.br</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">David</namePart><namePart type="family">Addiss</namePart><affiliation>Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">John</namePart><namePart type="family">Williamson</namePart><affiliation>Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Joaquim</namePart><namePart type="family">Norões</namePart><affiliation>NEPAF, Hospital das Clínicas, Universidade Federal de Pernambuco, Av. Prof. Moraes Rego s/n, Cidade Universitária, CEP 50740-900, Recife PE, Brazil</affiliation><affiliation>Departmento de Cirurgia, Hospital das Clínicas, Universidade Federal de Pernambuco, Recife PE, Brazil</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><originInfo><publisher>Royal Society of Tropical Medicine and Hygiene</publisher><dateIssued encoding="w3cdtf">2006-12</dateIssued><copyrightDate encoding="w3cdtf">2006</copyrightDate></originInfo><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>Although diethylcarbamazine (DEC) and albendazole are recommended to interrupt transmission of Wuchereria bancrofti, little is known about the macrofilaricidal effect of this drug combination. Forty-seven men with W. bancrofti infection were randomly assigned to receive a single dose of either DEC alone (6 mg/kg) (n = 25) or a combination of DEC (6 mg/kg) and albendazole (400 mg) (n = 22). Physical examinations for scrotal nodules (resulting from worm death) and ultrasound examinations (to detect living adult worms) were performed before treatment and 7, 14, 30, 45, 60, 90, 180, 270 and 360 days after treatment. Blood was examined for microfilariae before and 30 days and 360 days after treatment. Seven days post treatment, intrascrotal nodules were detected at the site of 21 (46.7%) adult worm nests in men who received DEC alone compared with 2 (6.1%) sites in men who received DEC and albendazole (P = 0.002). One year after treatment, 10 (22.2%) original adult worm nests remained detectable by ultrasound among men who received DEC alone compared with 18/32 (56.3%) nests among men who received both drugs (P = 0.016). Microfilaraemia prevalence and density decreased to a similar extent in both groups. Addition of albendazole appeared to decrease the macrofilaricidal effect of DEC against W. bancrofti, with no detectable enhancement in microfilarial suppression.</abstract><subject lang="en"><genre>Keywords</genre><topic>Lymphatic filariasis</topic><topic>Albendazole</topic><topic>Diethylcarbamazine</topic><topic>Macrofilaricidal effect</topic><topic>Microfilaria</topic></subject><relatedItem type="host"><titleInfo><title>Transactions of The Royal Society of Tropical Medicine and Hygiene</title></titleInfo><titleInfo type="abbreviated"><title>Trans R Soc Trop Med Hyg</title></titleInfo><genre type="journal">journal</genre><identifier type="ISSN">0035-9203</identifier><identifier type="eISSN">1878-3503</identifier><identifier type="PublisherID">trstmh</identifier><identifier type="PublisherID-hwp">trstmh</identifier><part><date>2006</date><detail type="volume"><caption>vol.</caption><number>100</number></detail><detail type="issue"><caption>no.</caption><number>12</number></detail><extent unit="pages"><start>1118</start><end>1125</end></extent></part></relatedItem><identifier type="istex">08BDB13FA4F7E3873CC5F56ADC64278EFCC04AA2</identifier><identifier type="DOI">10.1016/j.trstmh.2006.04.006</identifier><recordInfo><recordContentSource>OUP</recordContentSource><recordOrigin>Royal Society of Tropical Medicine and Hygiene</recordOrigin></recordInfo></mods></metadata><covers><json:item><extension>tiff</extension><original>true</original><mimetype>image/tiff</mimetype><uri>https://api.istex.fr/document/08BDB13FA4F7E3873CC5F56ADC64278EFCC04AA2/covers/tiff</uri></json:item></covers><annexes><json:item><extension>jpeg</extension><original>true</original><mimetype>image/jpeg</mimetype><uri>https://api.istex.fr/document/08BDB13FA4F7E3873CC5F56ADC64278EFCC04AA2/annexes/jpeg</uri></json:item><json:item><extension>gif</extension><original>true</original><mimetype>image/gif</mimetype><uri>https://api.istex.fr/document/08BDB13FA4F7E3873CC5F56ADC64278EFCC04AA2/annexes/gif</uri></json:item></annexes><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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