Effect of a single dose of 8 mg moxidectin or 150 [mu]g/kg ivermectin on O. volvulus skin microfilariae in a randomized trial: Differences between areas in the Democratic Republic of the Congo, Liberia and Ghana and impact of intensity of infection

Background Our study in CDTI-naïve areas in Nord Kivu and Ituri (Democratic Republic of the Congo, DRC), Lofa County (Liberia) and Nkwanta district (Ghana) showed that a single 8 mg moxidectin dose reduced skin microfilariae density (microfilariae/mg skin, SmfD) better and for longer than a single 1...

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Veröffentlicht in:PLoS neglected tropical diseases 2022-04, Vol.16 (4)
Hauptverfasser: Bakajika, Didier, Kanza, Eric M, Opoku, Nicholas O, Howard, Hayford M, Mambandu, Germain L, Nyathirombo, Amos, Nigo, Maurice M, Kennedy, Kambale Kasonia, Masembe, Safari L, Mumbere, Mupenzi, Kataliko, Kambale, Bolay, Kpehe M, Attah, Simon K, Olipoh, George, Asare, Sampson, Vaillant, Michel, Halleux, Christine M, Kuesel, Annette C
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container_issue 4
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container_title PLoS neglected tropical diseases
container_volume 16
creator Bakajika, Didier
Kanza, Eric M
Opoku, Nicholas O
Howard, Hayford M
Mambandu, Germain L
Nyathirombo, Amos
Nigo, Maurice M
Kennedy, Kambale Kasonia
Masembe, Safari L
Mumbere, Mupenzi
Kataliko, Kambale
Bolay, Kpehe M
Attah, Simon K
Olipoh, George
Asare, Sampson
Vaillant, Michel
Halleux, Christine M
Kuesel, Annette C
description Background Our study in CDTI-naïve areas in Nord Kivu and Ituri (Democratic Republic of the Congo, DRC), Lofa County (Liberia) and Nkwanta district (Ghana) showed that a single 8 mg moxidectin dose reduced skin microfilariae density (microfilariae/mg skin, SmfD) better and for longer than a single 150[mu]g/kg ivermectin dose. We now analysed efficacy by study area and pre-treatment SmfD (intensity of infection, IoI). Methodology/Principal findings Four and three IoI categories were defined for across-study and by-study area analyses, respectively. We used a general linear model to analyse SmfD 1, 6, 12 and 18 months post-treatment, a logistic model to determine the odds of undetectable SmfD from month 1 to month 6 (UD1-6), month 12 (UD1-12) and month 18 (UD1-18), and descriptive statistics to quantitate inter-interindividual response differences. Twelve months post-treatment, treatment differences (difference in adjusted geometric mean SmfD after moxidectin and ivermectin in percentage of the adjusted geometric mean SmfD after ivermectin treatment) were 92.9%, 90.1%, 86.8% and 84.5% in Nord Kivu, Ituri, Lofa and Nkwanta, and 74.1%, 84.2%, 90.0% and 95.4% for participants with SmfD 10-20, [greater than or equal to]20-
doi_str_mv 10.1371/journal.pntd.0010079
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We now analysed efficacy by study area and pre-treatment SmfD (intensity of infection, IoI). Methodology/Principal findings Four and three IoI categories were defined for across-study and by-study area analyses, respectively. We used a general linear model to analyse SmfD 1, 6, 12 and 18 months post-treatment, a logistic model to determine the odds of undetectable SmfD from month 1 to month 6 (UD1-6), month 12 (UD1-12) and month 18 (UD1-18), and descriptive statistics to quantitate inter-interindividual response differences. Twelve months post-treatment, treatment differences (difference in adjusted geometric mean SmfD after moxidectin and ivermectin in percentage of the adjusted geometric mean SmfD after ivermectin treatment) were 92.9%, 90.1%, 86.8% and 84.5% in Nord Kivu, Ituri, Lofa and Nkwanta, and 74.1%, 84.2%, 90.0% and 95.4% for participants with SmfD 10-20, [greater than or equal to]20-&lt;50, [greater than or equal to]50-&lt;80, [greater than or equal to]80, respectively. Ivermectin's efficacy was lower in Ituri and Nkwanta than Nord Kivu and Lofa (p[less than or equal to]0.002) and moxidectin's efficacy lower in Nkwanta than Nord Kivu, Ituri and Lofa (p40% of pre-treatment SmfD) occurred in 0%, 0.3%, 1.6% and 3.9% of moxidectin and 12.1%, 23.7%, 10.8% and 28.0% of ivermectin treated participants in Nord Kivu, Ituri, Lofa and Nkwanta, respectively. Conclusions/Significance The benefit of moxidectin vs ivermectin treatment increased with pre-treatment IoI. The possibility that parasite populations in different areas have different drug susceptibility without prior ivermectin selection pressure needs to be considered and further investigated. Clinical Trial Registration Registered on 14 November 2008 in Clinicaltrials.gov (ID: NCT00790998).</description><identifier>ISSN: 1935-2727</identifier><identifier>DOI: 10.1371/journal.pntd.0010079</identifier><language>eng</language><publisher>Public Library of Science</publisher><subject>Care and treatment ; Diagnosis ; Dosage and administration ; Ivermectin ; Onchocerciasis ; Risk factors</subject><ispartof>PLoS neglected tropical diseases, 2022-04, Vol.16 (4)</ispartof><rights>COPYRIGHT 2022 Public Library of Science</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,864,27924,27925</link.rule.ids></links><search><creatorcontrib>Bakajika, Didier</creatorcontrib><creatorcontrib>Kanza, Eric M</creatorcontrib><creatorcontrib>Opoku, Nicholas O</creatorcontrib><creatorcontrib>Howard, Hayford M</creatorcontrib><creatorcontrib>Mambandu, Germain L</creatorcontrib><creatorcontrib>Nyathirombo, Amos</creatorcontrib><creatorcontrib>Nigo, Maurice M</creatorcontrib><creatorcontrib>Kennedy, Kambale Kasonia</creatorcontrib><creatorcontrib>Masembe, Safari L</creatorcontrib><creatorcontrib>Mumbere, Mupenzi</creatorcontrib><creatorcontrib>Kataliko, Kambale</creatorcontrib><creatorcontrib>Bolay, Kpehe M</creatorcontrib><creatorcontrib>Attah, Simon K</creatorcontrib><creatorcontrib>Olipoh, George</creatorcontrib><creatorcontrib>Asare, Sampson</creatorcontrib><creatorcontrib>Vaillant, Michel</creatorcontrib><creatorcontrib>Halleux, Christine M</creatorcontrib><creatorcontrib>Kuesel, Annette C</creatorcontrib><title>Effect of a single dose of 8 mg moxidectin or 150 [mu]g/kg ivermectin on O. volvulus skin microfilariae in a randomized trial: Differences between areas in the Democratic Republic of the Congo, Liberia and Ghana and impact of intensity of infection</title><title>PLoS neglected tropical diseases</title><description>Background Our study in CDTI-naïve areas in Nord Kivu and Ituri (Democratic Republic of the Congo, DRC), Lofa County (Liberia) and Nkwanta district (Ghana) showed that a single 8 mg moxidectin dose reduced skin microfilariae density (microfilariae/mg skin, SmfD) better and for longer than a single 150[mu]g/kg ivermectin dose. We now analysed efficacy by study area and pre-treatment SmfD (intensity of infection, IoI). Methodology/Principal findings Four and three IoI categories were defined for across-study and by-study area analyses, respectively. We used a general linear model to analyse SmfD 1, 6, 12 and 18 months post-treatment, a logistic model to determine the odds of undetectable SmfD from month 1 to month 6 (UD1-6), month 12 (UD1-12) and month 18 (UD1-18), and descriptive statistics to quantitate inter-interindividual response differences. Twelve months post-treatment, treatment differences (difference in adjusted geometric mean SmfD after moxidectin and ivermectin in percentage of the adjusted geometric mean SmfD after ivermectin treatment) were 92.9%, 90.1%, 86.8% and 84.5% in Nord Kivu, Ituri, Lofa and Nkwanta, and 74.1%, 84.2%, 90.0% and 95.4% for participants with SmfD 10-20, [greater than or equal to]20-&lt;50, [greater than or equal to]50-&lt;80, [greater than or equal to]80, respectively. Ivermectin's efficacy was lower in Ituri and Nkwanta than Nord Kivu and Lofa (p[less than or equal to]0.002) and moxidectin's efficacy lower in Nkwanta than Nord Kivu, Ituri and Lofa (p40% of pre-treatment SmfD) occurred in 0%, 0.3%, 1.6% and 3.9% of moxidectin and 12.1%, 23.7%, 10.8% and 28.0% of ivermectin treated participants in Nord Kivu, Ituri, Lofa and Nkwanta, respectively. Conclusions/Significance The benefit of moxidectin vs ivermectin treatment increased with pre-treatment IoI. The possibility that parasite populations in different areas have different drug susceptibility without prior ivermectin selection pressure needs to be considered and further investigated. Clinical Trial Registration Registered on 14 November 2008 in Clinicaltrials.gov (ID: NCT00790998).</description><subject>Care and treatment</subject><subject>Diagnosis</subject><subject>Dosage and administration</subject><subject>Ivermectin</subject><subject>Onchocerciasis</subject><subject>Risk factors</subject><issn>1935-2727</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid/><recordid>eNptUE1v1DAQzQEkSuEfcBgJiROb2km8jrlV21KQVqqEekOocuxJ1q0_VrazBX55j3W0PRQJ-eDxm_fe-E1VfaCkpi2nZ3dhjl7aeu-zrgmhhHDxqjqhomWrhjf8TfU2pTtCmGA9PakeL8cRVYYwgoRk_GQRdEi4AD24CVz4bXRhGA8hAmUEfrr513R2P4E5YHTPLQ_XNRyCPcx2TpDuC-aMimE0VkYjEQogIUqvgzN_UUMuqP0CF6bMj-gVJhgwPyAWXkSZFkHeIVygCyrKbBT8wP082FKUvy2tTfBT-AxbM2Axg-INVzvpj5Vxe3nMZXxGn0z-c3wscU3w76rXo7QJ3z_fp9XN18ubzbfV9vrq--Z8u5pET1dKrTs2Eo1No8vyFNG0Fa3qUawVGblmgrcFW_Oecz6wgXTd2FLWt4NWXSdIe1p9PNpO0uJtmR5ylMqZpG7POWmYoHxNC6v-D6scjWWLwWNZI_4r-PRCsENp8y4FOy_J0kviE-XgqSA</recordid><startdate>20220427</startdate><enddate>20220427</enddate><creator>Bakajika, Didier</creator><creator>Kanza, Eric M</creator><creator>Opoku, Nicholas O</creator><creator>Howard, Hayford M</creator><creator>Mambandu, Germain L</creator><creator>Nyathirombo, Amos</creator><creator>Nigo, Maurice M</creator><creator>Kennedy, Kambale Kasonia</creator><creator>Masembe, Safari L</creator><creator>Mumbere, Mupenzi</creator><creator>Kataliko, Kambale</creator><creator>Bolay, Kpehe M</creator><creator>Attah, Simon K</creator><creator>Olipoh, George</creator><creator>Asare, Sampson</creator><creator>Vaillant, Michel</creator><creator>Halleux, Christine M</creator><creator>Kuesel, Annette C</creator><general>Public Library of Science</general><scope/></search><sort><creationdate>20220427</creationdate><title>Effect of a single dose of 8 mg moxidectin or 150 [mu]g/kg ivermectin on O. volvulus skin microfilariae in a randomized trial: Differences between areas in the Democratic Republic of the Congo, Liberia and Ghana and impact of intensity of infection</title><author>Bakajika, Didier ; Kanza, Eric M ; Opoku, Nicholas O ; Howard, Hayford M ; Mambandu, Germain L ; Nyathirombo, Amos ; Nigo, Maurice M ; Kennedy, Kambale Kasonia ; Masembe, Safari L ; Mumbere, Mupenzi ; Kataliko, Kambale ; Bolay, Kpehe M ; Attah, Simon K ; Olipoh, George ; Asare, Sampson ; Vaillant, Michel ; Halleux, Christine M ; Kuesel, Annette C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g981-cc645f0de22d727c0d1393c8e96c0f7d59730d1678777b5b044f31583bdc44903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Care and treatment</topic><topic>Diagnosis</topic><topic>Dosage and administration</topic><topic>Ivermectin</topic><topic>Onchocerciasis</topic><topic>Risk factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bakajika, Didier</creatorcontrib><creatorcontrib>Kanza, Eric M</creatorcontrib><creatorcontrib>Opoku, Nicholas O</creatorcontrib><creatorcontrib>Howard, Hayford M</creatorcontrib><creatorcontrib>Mambandu, Germain L</creatorcontrib><creatorcontrib>Nyathirombo, Amos</creatorcontrib><creatorcontrib>Nigo, Maurice M</creatorcontrib><creatorcontrib>Kennedy, Kambale Kasonia</creatorcontrib><creatorcontrib>Masembe, Safari L</creatorcontrib><creatorcontrib>Mumbere, Mupenzi</creatorcontrib><creatorcontrib>Kataliko, Kambale</creatorcontrib><creatorcontrib>Bolay, Kpehe M</creatorcontrib><creatorcontrib>Attah, Simon K</creatorcontrib><creatorcontrib>Olipoh, George</creatorcontrib><creatorcontrib>Asare, Sampson</creatorcontrib><creatorcontrib>Vaillant, Michel</creatorcontrib><creatorcontrib>Halleux, Christine M</creatorcontrib><creatorcontrib>Kuesel, Annette C</creatorcontrib><jtitle>PLoS neglected tropical diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bakajika, Didier</au><au>Kanza, Eric M</au><au>Opoku, Nicholas O</au><au>Howard, Hayford M</au><au>Mambandu, Germain L</au><au>Nyathirombo, Amos</au><au>Nigo, Maurice M</au><au>Kennedy, Kambale Kasonia</au><au>Masembe, Safari L</au><au>Mumbere, Mupenzi</au><au>Kataliko, Kambale</au><au>Bolay, Kpehe M</au><au>Attah, Simon K</au><au>Olipoh, George</au><au>Asare, Sampson</au><au>Vaillant, Michel</au><au>Halleux, Christine M</au><au>Kuesel, Annette C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of a single dose of 8 mg moxidectin or 150 [mu]g/kg ivermectin on O. volvulus skin microfilariae in a randomized trial: Differences between areas in the Democratic Republic of the Congo, Liberia and Ghana and impact of intensity of infection</atitle><jtitle>PLoS neglected tropical diseases</jtitle><date>2022-04-27</date><risdate>2022</risdate><volume>16</volume><issue>4</issue><issn>1935-2727</issn><abstract>Background Our study in CDTI-naïve areas in Nord Kivu and Ituri (Democratic Republic of the Congo, DRC), Lofa County (Liberia) and Nkwanta district (Ghana) showed that a single 8 mg moxidectin dose reduced skin microfilariae density (microfilariae/mg skin, SmfD) better and for longer than a single 150[mu]g/kg ivermectin dose. We now analysed efficacy by study area and pre-treatment SmfD (intensity of infection, IoI). Methodology/Principal findings Four and three IoI categories were defined for across-study and by-study area analyses, respectively. We used a general linear model to analyse SmfD 1, 6, 12 and 18 months post-treatment, a logistic model to determine the odds of undetectable SmfD from month 1 to month 6 (UD1-6), month 12 (UD1-12) and month 18 (UD1-18), and descriptive statistics to quantitate inter-interindividual response differences. Twelve months post-treatment, treatment differences (difference in adjusted geometric mean SmfD after moxidectin and ivermectin in percentage of the adjusted geometric mean SmfD after ivermectin treatment) were 92.9%, 90.1%, 86.8% and 84.5% in Nord Kivu, Ituri, Lofa and Nkwanta, and 74.1%, 84.2%, 90.0% and 95.4% for participants with SmfD 10-20, [greater than or equal to]20-&lt;50, [greater than or equal to]50-&lt;80, [greater than or equal to]80, respectively. Ivermectin's efficacy was lower in Ituri and Nkwanta than Nord Kivu and Lofa (p[less than or equal to]0.002) and moxidectin's efficacy lower in Nkwanta than Nord Kivu, Ituri and Lofa (p40% of pre-treatment SmfD) occurred in 0%, 0.3%, 1.6% and 3.9% of moxidectin and 12.1%, 23.7%, 10.8% and 28.0% of ivermectin treated participants in Nord Kivu, Ituri, Lofa and Nkwanta, respectively. Conclusions/Significance The benefit of moxidectin vs ivermectin treatment increased with pre-treatment IoI. The possibility that parasite populations in different areas have different drug susceptibility without prior ivermectin selection pressure needs to be considered and further investigated. Clinical Trial Registration Registered on 14 November 2008 in Clinicaltrials.gov (ID: NCT00790998).</abstract><pub>Public Library of Science</pub><doi>10.1371/journal.pntd.0010079</doi></addata></record>
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subjects Care and treatment
Diagnosis
Dosage and administration
Ivermectin
Onchocerciasis
Risk factors
title Effect of a single dose of 8 mg moxidectin or 150 [mu]g/kg ivermectin on O. volvulus skin microfilariae in a randomized trial: Differences between areas in the Democratic Republic of the Congo, Liberia and Ghana and impact of intensity of infection
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