Long-term effect of three different strategies for mass diethylcarbamazine administration in bancroftian filariasis: follow-up at 10 years after treatment
Identifieur interne : 003331 ( Istex/Corpus ); précédent : 003330; suivant : 003332Long-term effect of three different strategies for mass diethylcarbamazine administration in bancroftian filariasis: follow-up at 10 years after treatment
Auteurs : Dan W. Meyrowitsch ; Paul E. Simonsen ; Stephen M. MagesaSource :
- Transactions of The Royal Society of Tropical Medicine and Hygiene [ 0035-9203 ] ; 2004-11.
English descriptors
Abstract
The long-term effect of three different strategies for mass diethylcarbamazine (DEC) administration in bancroftian filariasis was assessed 10 years after start of treatment in three endemic communities in Tanzania. The strategies were the standard 12 day treatment (strategy I); a semi-annual single-dose treatment (strategy II); and a monthly low-dose treatment (strategy III). Treatment was given only during the first year. Following reductions immediately after treatment, overall community microfilaraemia levels were approaching pre-treatment levels in all three communities, 10 years later. In individuals who were microfilaria-positive and treated at baseline, the treatment had a long-term effect on microfilarial intensities, with geometric mean intensities being only 11%, 13% and 2% of pre-treatment levels 10 years later for strategies I, II and III, respectively. This suppressive effect was most pronounced for strategy III, which also cleared microfilaraemia and circulating filarial antigenaemia in a larger proportion of treated individuals than the other strategies. Most of the follow-up individuals who developed microfilaraemia between 2 and 10 years after start of treatment had also been microfilaraemic before treatment, suggesting that reappearance of microfilaraemia may be due to surviving female worms and/or that previously microfilaraemic individuals have a higher chance of reinfection than previously amicrofilaraemic individuals.
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DOI: 10.1016/j.trstmh.2004.01.004
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ISTEX:6D892453149FB4991FE7F4300A76177388FEB0F3Le document en format XML
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Meyrowitsch</name><affiliation><mods:affiliation>Department of Epidemiology, Institute of Public Health, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: d.meyrowitsch@pubhealth.ku.dk</mods:affiliation></affiliation></author><author><name sortKey="Simonsen, Paul E" sort="Simonsen, Paul E" uniqKey="Simonsen P" first="Paul E." last="Simonsen">Paul E. Simonsen</name><affiliation><mods:affiliation>Danish Bilharziasis Laboratory, Jaegersborg Alle 1D, 2920 Charlottenlund, Denmark</mods:affiliation></affiliation></author><author><name sortKey="Magesa, Stephen M" sort="Magesa, Stephen M" uniqKey="Magesa S" first="Stephen M." last="Magesa">Stephen M. Magesa</name><affiliation><mods:affiliation>National Institute for Medical Research, Ubwari Research Station, P.O. Box 81, Muheza, Tanzania</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="2004-11">2004-11</date><biblScope unit="volume">98</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="627">627</biblScope><biblScope unit="page" to="634">634</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>Control</term><term>Diethylcarbamazine</term><term>Filariasis</term><term>Mass drug administration</term><term>Tanzania</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract">The long-term effect of three different strategies for mass diethylcarbamazine (DEC) administration in bancroftian filariasis was assessed 10 years after start of treatment in three endemic communities in Tanzania. The strategies were the standard 12 day treatment (strategy I); a semi-annual single-dose treatment (strategy II); and a monthly low-dose treatment (strategy III). Treatment was given only during the first year. Following reductions immediately after treatment, overall community microfilaraemia levels were approaching pre-treatment levels in all three communities, 10 years later. In individuals who were microfilaria-positive and treated at baseline, the treatment had a long-term effect on microfilarial intensities, with geometric mean intensities being only 11%, 13% and 2% of pre-treatment levels 10 years later for strategies I, II and III, respectively. This suppressive effect was most pronounced for strategy III, which also cleared microfilaraemia and circulating filarial antigenaemia in a larger proportion of treated individuals than the other strategies. Most of the follow-up individuals who developed microfilaraemia between 2 and 10 years after start of treatment had also been microfilaraemic before treatment, suggesting that reappearance of microfilaraemia may be due to surviving female worms and/or that previously microfilaraemic individuals have a higher chance of reinfection than previously amicrofilaraemic individuals.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Dan W. Meyrowitsch</name><affiliations><json:string>Department of Epidemiology, Institute of Public Health, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark</json:string><json:string>E-mail: d.meyrowitsch@pubhealth.ku.dk</json:string></affiliations></json:item><json:item><name>Paul E. Simonsen</name><affiliations><json:string>Danish Bilharziasis Laboratory, Jaegersborg Alle 1D, 2920 Charlottenlund, Denmark</json:string></affiliations></json:item><json:item><name>Stephen M. Magesa</name><affiliations><json:string>National Institute for Medical Research, Ubwari Research Station, P.O. Box 81, Muheza, Tanzania</json:string></affiliations></json:item></author><subject><json:item><value>Filariasis</value></json:item><json:item><value>Control</value></json:item><json:item><value>Mass drug administration</value></json:item><json:item><value>Diethylcarbamazine</value></json:item><json:item><value>Tanzania</value></json:item></subject><language><json:string>unknown</json:string></language><originalGenre><json:string>research-article</json:string></originalGenre><abstract>The long-term effect of three different strategies for mass diethylcarbamazine (DEC) administration in bancroftian filariasis was assessed 10 years after start of treatment in three endemic communities in Tanzania. The strategies were the standard 12 day treatment (strategy I); a semi-annual single-dose treatment (strategy II); and a monthly low-dose treatment (strategy III). Treatment was given only during the first year. Following reductions immediately after treatment, overall community microfilaraemia levels were approaching pre-treatment levels in all three communities, 10 years later. In individuals who were microfilaria-positive and treated at baseline, the treatment had a long-term effect on microfilarial intensities, with geometric mean intensities being only 11%, 13% and 2% of pre-treatment levels 10 years later for strategies I, II and III, respectively. This suppressive effect was most pronounced for strategy III, which also cleared microfilaraemia and circulating filarial antigenaemia in a larger proportion of treated individuals than the other strategies. Most of the follow-up individuals who developed microfilaraemia between 2 and 10 years after start of treatment had also been microfilaraemic before treatment, suggesting that reappearance of microfilaraemia may be due to surviving female worms and/or that previously microfilaraemic individuals have a higher chance of reinfection than previously amicrofilaraemic individuals.</abstract><qualityIndicators><score>8.434</score><pdfVersion>1.3</pdfVersion><pdfPageSize>595 x 793 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>5</keywordCount><abstractCharCount>1463</abstractCharCount><pdfWordCount>4046</pdfWordCount><pdfCharCount>27141</pdfCharCount><pdfPageCount>8</pdfPageCount><abstractWordCount>199</abstractWordCount></qualityIndicators><title>Long-term effect of three different strategies for mass diethylcarbamazine administration in bancroftian filariasis: follow-up at 10 years after treatment</title><genre><json:string>research-article</json:string></genre><host><title>Transactions of The Royal Society of Tropical Medicine and Hygiene</title><language><json:string>unknown</json:string></language><issn><json:string>0035-9203</json:string></issn><eissn><json:string>1878-3503</json:string></eissn><publisherId><json:string>trstmh</json:string></publisherId><volume>98</volume><issue>11</issue><pages><first>627</first><last>634</last></pages><genre><json:string>journal</json:string></genre></host><categories><wos><json:string>social science</json:string><json:string>public, environmental & occupational health</json:string><json:string>science</json:string><json:string>tropical medicine</json:string></wos><scienceMetrix><json:string>health sciences</json:string><json:string>clinical medicine</json:string><json:string>tropical medicine</json:string></scienceMetrix><inist><json:string>sciences appliquees, technologies et medecines</json:string><json:string>sciences biologiques et medicales</json:string><json:string>sciences medicales</json:string></inist></categories><publicationDate>2004</publicationDate><copyrightDate>2004</copyrightDate><doi><json:string>10.1016/j.trstmh.2004.01.004</json:string></doi><id>6D892453149FB4991FE7F4300A76177388FEB0F3</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/6D892453149FB4991FE7F4300A76177388FEB0F3/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/6D892453149FB4991FE7F4300A76177388FEB0F3/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/6D892453149FB4991FE7F4300A76177388FEB0F3/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Long-term effect of three different strategies for mass diethylcarbamazine administration in bancroftian filariasis: follow-up at 10 years after treatment</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Royal Society of Tropical Medicine and Hygiene</publisher><availability><p>OUP</p></availability><date>2004</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Long-term effect of three different strategies for mass diethylcarbamazine administration in bancroftian filariasis: follow-up at 10 years after treatment</title><author xml:id="author-0000" corresp="yes"><persName><forename type="first">Dan W.</forename><surname>Meyrowitsch</surname></persName><email>d.meyrowitsch@pubhealth.ku.dk</email><affiliation>Department of Epidemiology, Institute of Public Health, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Paul E.</forename><surname>Simonsen</surname></persName><affiliation>Danish Bilharziasis Laboratory, Jaegersborg Alle 1D, 2920 Charlottenlund, Denmark</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Stephen M.</forename><surname>Magesa</surname></persName><affiliation>National Institute for Medical Research, Ubwari Research Station, P.O. Box 81, Muheza, Tanzania</affiliation></author><idno type="istex">6D892453149FB4991FE7F4300A76177388FEB0F3</idno><idno type="DOI">10.1016/j.trstmh.2004.01.004</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="2004-11"></date><biblScope unit="volume">98</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="627">627</biblScope><biblScope unit="page" to="634">634</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2004</date></creation><abstract><p>The long-term effect of three different strategies for mass diethylcarbamazine (DEC) administration in bancroftian filariasis was assessed 10 years after start of treatment in three endemic communities in Tanzania. The strategies were the standard 12 day treatment (strategy I); a semi-annual single-dose treatment (strategy II); and a monthly low-dose treatment (strategy III). Treatment was given only during the first year. Following reductions immediately after treatment, overall community microfilaraemia levels were approaching pre-treatment levels in all three communities, 10 years later. In individuals who were microfilaria-positive and treated at baseline, the treatment had a long-term effect on microfilarial intensities, with geometric mean intensities being only 11%, 13% and 2% of pre-treatment levels 10 years later for strategies I, II and III, respectively. This suppressive effect was most pronounced for strategy III, which also cleared microfilaraemia and circulating filarial antigenaemia in a larger proportion of treated individuals than the other strategies. Most of the follow-up individuals who developed microfilaraemia between 2 and 10 years after start of treatment had also been microfilaraemic before treatment, suggesting that reappearance of microfilaraemia may be due to surviving female worms and/or that previously microfilaraemic individuals have a higher chance of reinfection than previously amicrofilaraemic individuals.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Filariasis</term></item><item><term>Control</term></item><item><term>Mass drug administration</term></item><item><term>Diethylcarbamazine</term></item><item><term>Tanzania</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2004-11">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/6D892453149FB4991FE7F4300A76177388FEB0F3/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>
<journal-meta>
<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>
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<article-meta>
<article-id pub-id-type="doi">10.1016/j.trstmh.2004.01.004</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Articles</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Long-term effect of three different strategies for mass diethylcarbamazine administration in bancroftian filariasis: follow-up at 10 years after treatment</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name><surname>Meyrowitsch</surname><given-names>Dan W.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>a</sup></xref><xref ref-type="corresp" rid="COR1"><sup>∗</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Simonsen</surname><given-names>Paul E.</given-names></name><xref ref-type="aff" rid="AFF2"><sup>b</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Magesa</surname><given-names>Stephen M.</given-names></name><xref ref-type="aff" rid="AFF3"><sup>c</sup></xref>
</contrib>
<aff id="AFF1">
<label>a</label>Department of Epidemiology, Institute of Public Health, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark</aff>
<aff id="AFF2">
<label>b</label>Danish Bilharziasis Laboratory, Jaegersborg Alle 1D, 2920 Charlottenlund, Denmark</aff>
<aff id="AFF3">
<label>c</label>National Institute for Medical Research, Ubwari Research Station, P.O. Box 81, Muheza, Tanzania</aff>
</contrib-group>
<author-notes>
<corresp id="COR1">
<label>*</label>Corresponding author. Tel.: +45 35 32 73 82; fax: +45 35 32 73 83. <italic>E-mail addresses:</italic> <email>d.meyrowitsch@pubhealth.ku.dk</email> (D.W. Meyrowitsch), <email>pes@bilharziasis.dk</email> (P.E. Simonsen), <email>smagesa@hotmail.com</email> (S.M. Magesa).</corresp>
</author-notes>
<pub-date pub-type="ppub">
<month>11</month>
<year>2004</year>
</pub-date>
<volume>98</volume>
<issue>11</issue>
<fpage>627</fpage>
<lpage>634</lpage>
<history>
<date date-type="received">
<day>6</day>
<month>10</month>
<year>2003</year></date>
<date date-type="rev-recd">
<day>23</day>
<month>12</month>
<year>2003</year></date>
<date date-type="accepted">
<day>12</day>
<month>1</month>
<year>2004</year></date>
</history>
<permissions>
<copyright-year>2004</copyright-year>
<copyright-holder>Royal Society of Tropical Medicine and Hygiene</copyright-holder>
</permissions>
<abstract>
<title>Abstract</title>
<p>The long-term effect of three different strategies for mass diethylcarbamazine (DEC) administration in bancroftian filariasis was assessed 10 years after start of treatment in three endemic communities in Tanzania. The strategies were the standard 12 day treatment (strategy I); a semi-annual single-dose treatment (strategy II); and a monthly low-dose treatment (strategy III). Treatment was given only during the first year. Following reductions immediately after treatment, overall community microfilaraemia levels were approaching pre-treatment levels in all three communities, 10 years later. In individuals who were microfilaria-positive and treated at baseline, the treatment had a long-term effect on microfilarial intensities, with geometric mean intensities being only 11%, 13% and 2% of pre-treatment levels 10 years later for strategies I, II and III, respectively. This suppressive effect was most pronounced for strategy III, which also cleared microfilaraemia and circulating filarial antigenaemia in a larger proportion of treated individuals than the other strategies. Most of the follow-up individuals who developed microfilaraemia between 2 and 10 years after start of treatment had also been microfilaraemic before treatment, suggesting that reappearance of microfilaraemia may be due to surviving female worms and/or that previously microfilaraemic individuals have a higher chance of reinfection than previously amicrofilaraemic individuals.</p>
</abstract>
<kwd-group xml:lang="en">
<title>Keywords</title>
<kwd>Filariasis</kwd>
<kwd><italic>Wuchereria bancrofti</italic></kwd>
<kwd>Control</kwd>
<kwd>Mass drug administration</kwd>
<kwd>Diethylcarbamazine</kwd>
<kwd>Tanzania</kwd>
</kwd-group>
</article-meta>
</front>
<body>
<sec>
<label>1</label>
<title>Introduction</title>
<p>Bancroftian filariasis, resulting from infection with the mosquito-borne filarial nematode <italic>Wuchereria bancrofti</italic>, affects more than 120 million people in tropical developing countries (<xref ref-type="bibr" rid="BIB15">Michael, 2000</xref>). The adult worms reside in the human lymphatic vessels where they elicit debilitating acute and chronic disease manifestations (e.g. hydrocele, lymphoedema and elephantiasis). The female worms release larvae called microfilariae (mf) which circulate in the blood. Increased awareness of the burden of suffering imposed by this infection in endemic populations has mobilized international efforts to promote and organize programmes for its control, through the Global Programme to Eliminate Lymphatic Filariasis (<xref ref-type="bibr" rid="BIB18">Ottesen, 2000</xref>).</p>
<p>Mass drug administration is the primary measure for control of bancroftian filariasis (<xref ref-type="bibr" rid="BIB19">Ottesen et al., 1997</xref>). The classic and best known antifilarial drug is diethylcarbamazine (DEC), which can effectively reduce the microfilarial load but which has a more limited effect on the adult worms (<xref ref-type="bibr" rid="BIB4">Dreyer et al., 1995</xref>; <xref ref-type="bibr" rid="BIB24">Simonsen et al., 2004</xref>). Most studies have assessed the effect of DEC during and shortly after treatment. In order to more fully understand the effect of DEC therapy in the patients, knowledge of the long-term effect is also of interest. Such information may furthermore help in the proper design of appropriate strategies for control programmes and for interpreting the outcome of these (<xref ref-type="bibr" rid="BIB16">Michael, 2002</xref>).</p>
<p>In 1992, a mass DEC administration trial assessing and comparing the effect of four different treatment strategies was initiated in four communities in an endemic area of northeastern Tanzania. The strategies were the standard 12 day treatment, a semi-annual single-dose treatment, a monthly low-dose treatment and DEC medicated salt treatment. Treatment took place during the first year only and no treatment was given thereafter. The results of the treatment after the first, second and fourth years have been reported previously (<xref ref-type="bibr" rid="BIB12">Meyrowitsch et al., 1996a</xref>,<xref ref-type="bibr" rid="BIB13">b</xref>,<xref ref-type="bibr" rid="BIB14">c</xref>; <xref ref-type="bibr" rid="BIB9">Meyrowitsch and Simonsen, 1998</xref>). Approximately 10 years after start of treatment, three of the communities were re-surveyed. All consenting individuals were examined for chronic clinical manifestations, microfilaraemia and circulating filarial antigenaemia. The fourth community, where the DEC medicated salt strategy had been applied, had meanwhile been given mass treatment with ivermectin, and was therefore excluded. This paper presents the findings and analyses the effect of treatment over the 10-year study period.</p>
</sec>
<sec sec-type="materials|methods">
<label>2</label>
<title>Materials and methods</title>
<sec>
<label>2.1</label>
<title>Study design</title>
<p>The study was carried out in three rural <italic>Wuchereria bancrofti</italic>-endemic communities, Tawalani, Kwale and Mkokora/Kwemkuna, in Tanga Region, north-eastern Tanzania. All consenting individuals aged ≥1 year were examined for chronic clinical manifestations of bancroftian filariasis and microfilaraemia, at pre-treatment in 1991 (<xref ref-type="bibr" rid="BIB10">Meyrowitsch et al., 1995a</xref>,<xref ref-type="bibr" rid="BIB11">b</xref>), and thereafter, in early 1992, they were offered treatment according to the strategy adopted for the community. Strategy I (given in Tawalani) was the standard treatment (6 mg DEC/kg bodyweight given once daily for 12 consecutive days). Strategy II (given in Kwale) was a semi-annual single-dose treatment (6 mg DEC/kg bodyweight) given once every 6 months for a period of one year (i.e. 3 single doses, the last given immediately after the one-year follow-up survey). Strategy III (given in Mkokora/Kwemkuna) was a monthly low-dose treatment (50 mg DEC to children <15 years old; 100 mg DEC to adults ≥15 years) given for a period of one year (i.e. 12 doses, the last given two weeks before the one year follow-up). Treatment took place during the first study year only, and no treatment was given subsequently. Detailed descriptions of survey methodologies, treatment procedures and post-treatment findings at 3, 6 and 12 months, and 2 and 4 years, after start of treatment have been given previously (<xref ref-type="bibr" rid="BIB12">Meyrowitsch et al., 1996a</xref>,<xref ref-type="bibr" rid="BIB13">b</xref>,<xref ref-type="bibr" rid="BIB14">c</xref>; <xref ref-type="bibr" rid="BIB9">Meyrowitsch and Simonsen, 1998</xref>).</p>
</sec>
<sec>
<label>2.2</label>
<title>The follow-up surveys at 10 years after start of treatment</title>
<p>The present follow-up surveys were carried out in late 2001, i.e. approximately 10 years after start of treatment, and included all consenting inhabitants of the three villages aged ≥1 year at the time of the survey. Of those examined at pre-treatment in 1991, 228 in Tawalani (46.7%), 335 in Kwale (42.1%) and 132 in Mkokora/Kwemkuna (41.3%) were also examined in 2001. Clinical and parasitological examination methodologies were similar to those used in the previous surveys. Briefly, chronic clinical manifestations of hydrocele and lymphoedema/elephantiasis were graded according to size and developmental stage, and males were interviewed about a possible history of hydrocelectomy. Microfilariae were quantified in 100 μl of finger-prick blood collected between 21:00 and 01:00 hours by using the counting chamber technique. To obtain further information about the infection status, individuals were also examined for <italic>W. bancrofti</italic>-specific circulating filarial antigen (CFA) by using the rapid ICT field test for blood specimens (NOW<sup>®</sup> ICT, Binax Inc., USA, Lot#005309). After completion of the surveys, all inhabitants from the three communities were offered treatment with a single dose of DEC (6 mg/kg bodyweight). The study was approved by the Medical Research Coordinating Committee of the National Institute for Medical Research in Tanzania.</p>
</sec>
<sec>
<label>2.3</label>
<title>Data analysis</title>
<p>Data were analysed by using the statistical software package SPSS 10.0 and as previously described (<xref ref-type="bibr" rid="BIB14">Meyrowitsch et al., 1996c</xref>). The geometric mean intensity (GMI) of microfilaraemias was calculated as antilog [<graphic mimetype="image" xlink:href="98-11-627-fig003.gif"></graphic>], with <italic>x</italic> being the number of mf/ml blood and <italic>n</italic> the number of individuals included in the calculation. When calculating community level mf GMIs, only the mf-positive individuals were included. When analysing mf GMIs in the cohorts of individuals who had been mf-positive at pre-treatment, those reverting to an amicrofilaraemic status were also included. <italic>P</italic> values of less than 0.05 were considered significant in statistical tests. Relative risks (RR) with 95% confidence intervals were calculated according to <xref ref-type="bibr" rid="BIB7">Kirkwood (1988)</xref>.</p>
</sec>
</sec>
<sec>
<label>3</label>
<title>Results</title>
<sec>
<label>3.1</label>
<title>Community findings at pre-treatment and 10 years after start of treatment</title>
<p>The overall community findings from the surveys carried out in Tawalani, Kwale and Mkokora/Kwemkuna at pre-treatment (late 1991) and 10 years after start of mass DEC administration (late 2001) are shown in <xref ref-type="fig" rid="TBL1">Table 1</xref>
<fig id="TBL1">
<label>Table 1</label>
<caption>
<p>Overall community results from the surveys in Tawalani, Kwale and Mkokora/Kwemkuna at pre-treatment (1991) and 10 years after start of mass DEC chemotherapy (late 2001)</p>
</caption>
<graphic mimetype="image" xlink:href="98-11-627-tbl001.tif"></graphic>
</fig>. Tawalani and Mkokora/Kwemkuna had an increase in population size over the 10-year period, whereas a slight reduction was seen in Kwale. The mf prevalences and mf GMIs were lower in 2001 than in 1991 in all three communities, but the differences were statistically significant only for prevalence in Tawalani (χ<sup>2</sup> test, <italic>P</italic> = 0.003) and for both of these indices in Mkokora/Kwemkuna (χ<sup>2</sup> test, <italic>P</italic> < 0.001; <italic>t</italic> test, <italic>P</italic> < 0.001). The prevalence of hydrocele in adult (≥20 years) males was significantly lower in 2001 than in 1991 in all three communities (χ<sup>2</sup> test, <italic>P</italic> < 0.05 for all tests), but the prevalence of lymphoedema in adult individuals did not differ significantly between surveys in any of the communities (χ<sup>2</sup> test, <italic>P</italic> > 0.05 for all tests). CFA prevalences were considerably higher than mf prevalences in all communities in 2001.</p>
</sec>
<sec>
<label>3.2</label>
<title>Effect of treatment in individuals who were microfilaraemic at pre-treatment</title>
<p>The treatment efficacy was assessed in 55, 40 and 42 individuals from Tawalani (strategy I), Kwale (strategy II) and Mkokora/Kwemkuna (strategy III) who were microfilaraemic at pre-treatment, completed the treatments, and attended the follow-up examinations at 1, 2, 4 and 10 years after start of treatment (<xref ref-type="fig" rid="TBL2">Table 2</xref>
<fig id="TBL2">
<label>Table 2</label>
<caption>
<p>The effect of DEC treatment on <italic>Wuchereria bancofti</italic> infection in individuals who were microfilaria positive at the pre-treatment survey. Only individuals who completed the treatment and follow-up examinations at 1, 2, 4 and 10 years are included</p>
</caption>
<graphic mimetype="image" xlink:href="98-11-627-tbl002.tif"></graphic>
</fig>). Maximum mf clearance rates and maximum reductions in mf GMIs were observed at 1 (strategy I) and 2 years (strategies II and III) after start of treatment (<xref ref-type="fig" rid="TBL2">Table 2</xref>, <xref ref-type="fig" rid="FIG1">Figure 1</xref>
<fig id="FIG1" position="float">
<label>Figure 1</label>
<caption>
<p>The effect of DEC chemotherapy on the prevalence (•) and geometric mean intensity (▴) of <italic>Wuchereria bancrofti</italic> microfilaraemia in individuals who were microfilaraemic during the pre-treatment survey. Strategy I (Tawalani), standard treatment; strategy II (Kwale), semi-annual single-dose treatment; strategy III (Mkokora/Kwemkuna), low monthly dose treatment.</p>
</caption>
<graphic mimetype="image" xlink:href="98-11-627-fig001.tif"></graphic>
</fig>). For strategy I, the mf clearance rates at 1, 2, 4 and 10 years did not differ significantly (χ<sup>2</sup> test, <italic>P</italic> > 0.05 for all tests). For strategies II and III, the mf clearance rates at 2 and 4 years did not differ significantly (χ<sup>2</sup> test, <italic>P</italic> > 0.05 for both tests), but significant increases occurred between 4 and 10 years (χ<sup>2</sup> test, <italic>P</italic> = 0.044 and <italic>P</italic> = 0.028 for strategies II and III, respectively). Microfilariae GMIs increased at a much slower rate than mf prevalences, and their reductions relative to pre-treatment values were still pronounced at 10 years after start of treatment (87.0–88.6% for strategies I and II; 97.6% for strategy III).</p>
<p>Almost all individuals who received treatment according to strategies I and II were still CFA-positive at the 10-year follow-up surveys (98.2 and 97.5%, respectively), whereas the CFA prevalence was lower among individuals who received treatment with strategy III (78.6%). This difference between strategies was even more striking when comparing the CFA prevalences in individuals who were amicrofilaraemic at the 10-year follow-up surveys (93.8–95.0% for strategies I and II; 50.0% for strategy III).</p>
</sec>
<sec>
<label>3.3</label>
<title>Development of microfilaraemia between the 2-year and the 10-year follow-up surveys</title>
<p>Many individuals who had cleared their microfilaraemia at the 2-year follow-up surveys were microfilaraemic again at 10 years. The individual appearance of microfilaraemia over these 8 years was clearly associated with the pre-treatment mf status (<xref ref-type="fig" rid="FIG2">Figure 2</xref>
<fig id="FIG2" position="float">
<label>Figure 2</label>
<caption>
<p>The rate of development of new cases of microfilaraemia between the follow-up surveys at 2 and 10 years in individuals ≥10 years old and either amicrofilaraemic (white bars) or microfilaraemic (black bars) at the pre-treatment surveys in 1991.</p>
</caption>
<graphic mimetype="image" xlink:href="98-11-627-fig002.tif"></graphic>
</fig>). Among individuals aged ≥10 years at baseline who were amicrofilaraemic at both pre-treatment and 2-year follow-up surveys, 6.7, 8.5 and 11.9% of strategy I, II and III treated individuals, respectively, were microfilaraemic at the 10-year follow-up, whereas among those who were microfilaraemic at pre-treatment but amicrofilaremic at the 2-year follow-up surveys, the corresponding rates of microfilaraemia at the 10-year follow-up surveys were 45.5, 50.0 and 56.7%. For all communities combined 8.5 and 51.2% of individuals who were amicrofilaraemic and microfilaraemic, respectively, at the pre-treatment surveys, and who were amicrofilaraemic at the 2-year follow-up surveys, developed microfilaraemia between the 2-year and 10-year follow-up surveys. Among those who were amicrofilaraemic at the 2-year follow-up surveys, presenting with mf at pre-treatment was thus a significant risk factor for being mf-positive at the 10-year follow-up (RR = 6.0; 95% CI 3.83–9.41).</p>
</sec>
<sec>
<label>3.4</label>
<title>Follow-up on clinical manifestations</title>
<p>A total of 21 males from the three communities combined had hydrocele at pre-treatment, completed the treatment, and did not have the hydrocele surgically removed during the study period. Eleven of these (52.4%) had no hydrocele at 10 years after start of treatment. Such complete disappearance was only seen in males who had small hydroceles (6–8 cm) at pre-treatment. Two and four males presented with either a less or a more advanced stage of hydrocele, respectively, whereas four males had a similar stage at the two surveys.</p>
<p>Eleven individuals from the three communities combined presented with leg lymphoedema at pre-treatment. In three of these (27.2%), the leg lymphoedema had disappeared at the 10-year follow-up surveys (all had stage II at pre-treatment). One and two individuals, respectively, had a less or a more advanced stage of lymphoedema and six individuals had a similar developmental stage at the two surveys.</p>
</sec>
</sec>
<sec>
<label>4</label>
<title>Discussion</title>
<p>The study communities were originally selected on the basis of relative stability and location away from main traffic routes. No major environmental changes to affect transmission of bancroftian filariasis had taken place in the study period, apart from the mass DEC administration described in the present paper. Tawalani and Mkokora/Kwemkuna showed a moderate increase in population size in the 10-year period, whereas Kwale had a slight decrease. It is likely that more young people left Kwale for jobs and education elsewhere, since this happened to be the most progressive community. In all three communities, however, the population turnover was more intense than indicated by the overall change in population size, with numerous births, many deaths and some migration in and out of the communities. For example, 23% of those examined in 2001 were below 10 years of age, and were therefore not present during the 1991 surveys. The overall community findings in 2001 should therefore be interpreted with caution. They should furthermore not be taken as a reflection of the outcome of a large-scale mass DEC administration-based control programme, since under such circumstances treatment would be given for longer periods and would also cover surrounding areas.</p>
<p>It is noteworthy, though, that despite marked reductions in community microfilaraemias during and immediately after treatment (<xref ref-type="bibr" rid="BIB14">Meyrowitsch et al., 1996c</xref>), these were again approaching pre-treatment levels in 2001. This was most obvious for Kwale (Strategy II), which also had the lowest pre-treatment mf prevalence and GMI, less pronounced for Tawalani (Strategy I), and least pronounced for Mokokora/Kwemkuna (Strategy III). The long-term reductions in microfilaraemia still visible in 2001 among pre-treatment mf-positive individuals were therefore counteracted by new infections appearing in others. The decrease in hydrocele prevalence among adult males in all communities was mainly due to a high number of hydrocelectomies performed in the period. There was no change in prevalence of leg lymphoedema, but only few cases were seen. The prevalence of CFA was much higher than the prevalence of mf, as also seen in other studies (<xref ref-type="bibr" rid="BIB22">Simonsen et al., 1996</xref>, <xref ref-type="bibr" rid="BIB23">2002</xref>), indicating that many more individuals were actually infected than those in whom mf were detected in the blood.</p>
<p>The long-term efficacy of treatment on microfilaraemia was analysed in three well-defined cohorts of individuals (representing the three communities/strategies), who were mf-positive at pre-treatment, and who had completed the treatments and attended all follow-up examinations. All three strategies had a marked effect on microfilaraemia in these cohorts, but the strategies differed with respect to the rate and magnitude of reductions in prevalence and intensity, and to the rate of increase after the maximum effect had been reached. Although lower numbers of individuals were included in the present analyses, findings for the first 4 years after start of treatment were similar to those reported previously (<xref ref-type="bibr" rid="BIB9">Meyrowitsch and Simonsen, 1998</xref>). At 10 years after start of treatment many individuals in the three cohorts were mf-positive (57–64%), and mf intensities were on the increase compared to the 4-year follow-up, but the mean mf intensities were still very low compared to pre-treatment levels. This remarkable long-term suppressive effect on mf intensities was obviously more profound for strategy III than for strategies I and II (97.5% vs. 87.0–88.6% reduction compared to pre-treatment).</p>
<p>Being CFA-positive is generally considered an indication of having an active infection, whether or not mf are present (<xref ref-type="bibr" rid="BIB8">McCarthy, 2000</xref>). In the strategy I and II cohorts, almost all individuals were CFA-positive at the 10-year follow-up, indicating active infection even in the majority of mf-free individuals. This could be due to either continued presence of adult worms from the original infection or reinfection. A similar persistence of CFA-positivity a long time after DEC treatment of mf-positive individuals has been reported from other studies (<xref ref-type="bibr" rid="BIB1">Beuria et al., 2002</xref>; <xref ref-type="bibr" rid="BIB20">Sahoo et al., 2002</xref>; <xref ref-type="bibr" rid="BIB21">Simonsen and Meyrowitsch, 1998</xref>). In contrast, in the strategy III cohort, a high proportion (50%) of the mf-negative individuals was CFA-negative at the 10-year follow-up. Strategy III therefore not only had a more effective long-term suppressive effect on microfilaraemias, but apparently also affected the adult worm survival more in the long term than the other two strategies. The total dose of DEC given to individuals in strategy III was of similar magnitude to that given in strategy II and much lower (by 3–4 times) than that given in strategy I. Studies on a shorter term have shown that low spaced-doses of DEC have a more pronounced suppressive effect on microfilaraemias than the standard 12 day regimen (<xref ref-type="bibr" rid="BIB5">Eberhard et al., 1991</xref>; <xref ref-type="bibr" rid="BIB14">Meyrowitsch et al., 1996c</xref>; <xref ref-type="bibr" rid="BIB9">Meyrowitsch and Simonsen, 1998</xref>), and it is likely that spacing of treatments is a key factor also for the higher long-term efficacy of strategy III compared to strategies I and II.</p>
<p>It was previously observed, among individuals aged ≥10 years at pre-treatment, that the vast majority of those who developed microfilaraemia between the 2-year and 4-year follow-up surveys were also microfilaraemic at pre-treatment (<xref ref-type="bibr" rid="BIB9">Meyrowitsch and Simonsen, 1998</xref>). This pattern was still clearly reflected at the present survey, although to a slightly lesser degree, probably because the length of the observation period had quadrupled (from 2 to 8 years). Thus, among individuals aged ≥10 years at pre-treatment and complying to the full study procedure, there was a six times higher risk of developing microfilaraemia between the 2-year and 10-year follow-up in those who had been microfilaraemic at pre-treatment compared to those who had been amicrofilaraemic (on average for the three communities). Others have similarly noticed a high rate of reacquisition of microfilaraemia following DEC treatment among previously microfilaraemic individuals (<xref ref-type="bibr" rid="BIB1">Beuria et al., 2002</xref>; <xref ref-type="bibr" rid="BIB3">Dissanayake, 1989</xref>; <xref ref-type="bibr" rid="BIB6">Gopinath et al., 1999</xref>; <xref ref-type="bibr" rid="BIB20">Sahoo et al., 2002</xref>). Diethycarbamazine is primarily a microfilaricidal drug, with a potential to also kill some, but usually not all, adult worms (<xref ref-type="bibr" rid="BIB4">Dreyer et al., 1995</xref>). With a mean reproductive age estimated to be 5–8 years (<xref ref-type="bibr" rid="BIB25">Vanamail et al., 1996</xref>), surviving adult worms may at least partly be responsible for the fast reappearence of microfilaraemia in previously mf-positive individuals after DEC treatment. An alternative, or additional, reason could be that previously microfilaraemic individuals have a higher chance for reinfection than previously amicrofilaraemic individuals, for example due to persisting parasite induced immunological tolerance (<xref ref-type="bibr" rid="BIB6">Gopinath et al., 1999</xref>), genetically based higher susceptibility (<xref ref-type="bibr" rid="BIB2">Choi et al., 2003</xref>), or more intense exposure to transmission (<xref ref-type="bibr" rid="BIB17">Michael et al., 2001</xref>).</p>
<p>An attempt was also made to assess the possible beneficial long-term effect of DEC administration on chronic clinical manifestations, but the number of previously seen cases attending the 10-year follow-up surveys was low, and many of the males who had hydrocele in 1991 had had a hydrocelectomy in the intervening period. The previously reported tendency for small hydroceles to have disappeared (<xref ref-type="bibr" rid="BIB14">Meyrowitsch et al., 1996c</xref>; <xref ref-type="bibr" rid="BIB9">Meyrowitsch and Simonsen, 1998</xref>) was still obvious and some small lymphoedemas had disappeared. However, the early stages of these manifestations are rather dynamic in nature, and their disappearance may not necessarily have been related to the treatment.</p>
<p>The present study documented a remarkable long-term effect of DEC treatment on microfilaraemia, with mean mf intensities among those treated still being considerably reduced compared to pre-treatment levels even at 10 years after treatment. This adds to its quality as an agent for long-term suppression of transmission in filariasis control programmes. Moreover, the study showed that the low monthly dose treatment had a more significant long-term effect on both mf and adult worms than the other two strategies, thus indicating that this strategy might be considered a promising alternative option for use in the efforts to control bancroftian filariasis.</p>
<sec>
<title>Conflicts of interest statement</title>
<p>The authors have no conflicts of interest concerning the work reported in this paper.</p>
</sec>
</sec>
</body>
<back>
<ack>
<title>Acknowledgements</title>
<p>We are grateful to the inhabitants of Tawalani, Kwale and Mkokora/Kwemkuna for their patience and co-operation in these surveys, and to the survey team from Bombo Field Station (M. Cosmas, C. Guzo, S. Hassani, J, Kivugo and C. Malimi) for dedicated assistance through many long days and nights. Dr M. Malecela-Lazaro (Director of Research and Training, National Institute for Medical Research, Tanzania) is thanked for her support. The study received financial support from the Council for Development Research (Danida), and the Danish Bilharziasis Laboratory, Denmark, and the paper is published with the permission of the Director General, National Institute for Medical Research, Tanzania.</p>
</ack>
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</article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Long-term effect of three different strategies for mass diethylcarbamazine administration in bancroftian filariasis: follow-up at 10 years after treatment</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Long-term effect of three different strategies for mass diethylcarbamazine administration in bancroftian filariasis: follow-up at 10 years after treatment</title></titleInfo><name type="personal" displayLabel="corresp"><namePart type="given">Dan W.</namePart><namePart type="family">Meyrowitsch</namePart><affiliation>Department of Epidemiology, Institute of Public Health, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark</affiliation><affiliation>E-mail: d.meyrowitsch@pubhealth.ku.dk</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Paul E.</namePart><namePart type="family">Simonsen</namePart><affiliation>Danish Bilharziasis Laboratory, Jaegersborg Alle 1D, 2920 Charlottenlund, Denmark</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Stephen M.</namePart><namePart type="family">Magesa</namePart><affiliation>National Institute for Medical Research, Ubwari Research Station, P.O. Box 81, Muheza, Tanzania</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">2004-11</dateIssued><copyrightDate encoding="w3cdtf">2004</copyrightDate></originInfo><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>The long-term effect of three different strategies for mass diethylcarbamazine (DEC) administration in bancroftian filariasis was assessed 10 years after start of treatment in three endemic communities in Tanzania. The strategies were the standard 12 day treatment (strategy I); a semi-annual single-dose treatment (strategy II); and a monthly low-dose treatment (strategy III). Treatment was given only during the first year. Following reductions immediately after treatment, overall community microfilaraemia levels were approaching pre-treatment levels in all three communities, 10 years later. In individuals who were microfilaria-positive and treated at baseline, the treatment had a long-term effect on microfilarial intensities, with geometric mean intensities being only 11%, 13% and 2% of pre-treatment levels 10 years later for strategies I, II and III, respectively. This suppressive effect was most pronounced for strategy III, which also cleared microfilaraemia and circulating filarial antigenaemia in a larger proportion of treated individuals than the other strategies. Most of the follow-up individuals who developed microfilaraemia between 2 and 10 years after start of treatment had also been microfilaraemic before treatment, suggesting that reappearance of microfilaraemia may be due to surviving female worms and/or that previously microfilaraemic individuals have a higher chance of reinfection than previously amicrofilaraemic individuals.</abstract><subject lang="en"><genre>Keywords</genre><topic>Filariasis</topic><topic>Control</topic><topic>Mass drug administration</topic><topic>Diethylcarbamazine</topic><topic>Tanzania</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>2004</date><detail type="volume"><caption>vol.</caption><number>98</number></detail><detail type="issue"><caption>no.</caption><number>11</number></detail><extent unit="pages"><start>627</start><end>634</end></extent></part></relatedItem><identifier type="istex">6D892453149FB4991FE7F4300A76177388FEB0F3</identifier><identifier type="DOI">10.1016/j.trstmh.2004.01.004</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/6D892453149FB4991FE7F4300A76177388FEB0F3/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/6D892453149FB4991FE7F4300A76177388FEB0F3/annexes/jpeg</uri></json:item><json:item><extension>gif</extension><original>true</original><mimetype>image/gif</mimetype><uri>https://api.istex.fr/document/6D892453149FB4991FE7F4300A76177388FEB0F3/annexes/gif</uri></json:item></annexes><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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