TY - JOUR
T1 - Effect of a single dose of 8 mg moxidectin or 150 μg/kg ivermectin on O. volvulus skin microfilariae in a randomized trial
T2 - Differences between areas in the Democratic Republic of the Congo, Liberia and Ghana and impact of intensity of infection
AU - Bakajika, Didier
AU - Kanza, Eric M.
AU - Opoku, Nicholas O.
AU - Howard, Hayford M.
AU - Mambandu, Germain L.
AU - Nyathirombo, Amos
AU - Nigo, Maurice M.
AU - Kennedy, Kambale Kasonia
AU - Masembe, Safari L.
AU - Mumbere, Mupenzi
AU - Kataliko, Kambale
AU - Bolay, Kpehe M.
AU - Attah, Simon K.
AU - Olipoh, George
AU - Asare, Sampson
AU - Vaillant, Michel
AU - Halleux, Christine M.
AU - Kuesel, Annette C.
N1 - Funding: WHO/TDR funded this study, utilizing contributions from the WHO African Programme for Onchocerciasis Control (APOC), 6.3 million $US from Wyeth and following its acquisition by Pfizer, Pfizer, and WHO/TDR donor countries. Wyeth provided drug for this study and contributed to the study protocol. Wyeth prepared the submissions to the Ministries of Health and provided data management services until July 3, 2011. Pfizer was not further involved in this study in any way, including data verification or analysis and has not commented on this manuscript.
PY - 2022/4/27
Y1 - 2022/4/27
N2 - 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 150μg/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, ≥20-<50, ≥50-<80, ≥80, respectively. Ivermectin's efficacy was lower in Ituri and Nkwanta than Nord Kivu and Lofa (p≤0.002) and moxidectin's efficacy lower in Nkwanta than Nord Kivu, Ituri and Lofa (p<0.006). Odds ratios for UD1-6, UD1-12 or UD1-18 after moxidectin versus ivermectin treatment exceeded 7.0. Suboptimal response (SmfD 12 months post-treatment >40% 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).
AB - 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 150μg/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, ≥20-<50, ≥50-<80, ≥80, respectively. Ivermectin's efficacy was lower in Ituri and Nkwanta than Nord Kivu and Lofa (p≤0.002) and moxidectin's efficacy lower in Nkwanta than Nord Kivu, Ituri and Lofa (p<0.006). Odds ratios for UD1-6, UD1-12 or UD1-18 after moxidectin versus ivermectin treatment exceeded 7.0. Suboptimal response (SmfD 12 months post-treatment >40% 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).
UR - https://www.scopus.com/pages/publications/85130003161
UR - https://pubmed.ncbi.nlm.nih.gov/35476631
U2 - 10.1371/journal.pntd.0010079
DO - 10.1371/journal.pntd.0010079
M3 - Article
C2 - 35476631
SN - 1935-2727
VL - 16
JO - PLoS Neglected Tropical Diseases
JF - PLoS Neglected Tropical Diseases
IS - 4
M1 - e0010079
ER -