Background
A single co-administered dose of ivermectin (IVM) plus diethylcarbamazine (DEC) plus albendazole (ALB), or triple-drug therapy, was recently found to be more effective for clearing microfilariae (Mf) than standard DEC plus ALB currently used for mass drug administration programs for lymphatic filariasis (LF) outside of sub-Saharan Africa. Triple-drug therapy has not been previously tested in LF-uninfected individuals from Africa. This study evaluated the pharmacokinetics (PK), safety, and efficacy of triple-drug therapy in people with and without
Wuchereria bancrofti
infection in West Africa.
Methods
In this open-label cohort study, treatment-naïve microfilaremic (>50 mf/mL, n = 32) and uninfected (circulating filarial antigen negative, n = 24) adults residing in Agboville district, Côte d’Ivoire, were treated with a single dose of IVM plus DEC plus ALB, and evaluated for adverse events (AEs) until 7 days post treatment. Drug levels were assessed by liquid chromatography and mass spectrometry. Persons responsible for assessing AEs were blinded to participants’ infection status.
Findings
There was no difference in AUC
0-inf
or C
max
between LF-infected and uninfected participants (P>0.05 for all comparisons). All subjects experienced mild AEs; 28% and 25% of infected and uninfected participants experienced grade 2 AEs, respectively. There were no severe or serious adverse events. Only fever (16 of 32 versus 4 of 24, P<0.001) and scrotal pain/swelling in males (6 of 20 versus 0 of 12, P = 0.025) were more frequent in infected than uninfected participants. All LF positive participants were amicrofilaremic at 7 days post-treatment and 27 of 31 (87%) remained amicrofilaremic 12 months after treatment.
Conclusions
Moderate to heavy
W
.
bancrofti
infection did not affect PK parameters for IVM, DEC or ALB following a single co-administered dose of these drugs compared to uninfected individuals. The drugs were well tolerated. This study confirmed the efficacy of the triple-drug therapy for clearing
W
.
bancrofti
Mf and has added important information to support the use of this regimen in LF elimination programs in areas of Africa without co-endemic onchocerciasis or loiasis.
Trial registration
ClinicalTrials.gov
NCT02845713
.
Deux lots d'alevins du tilapia Oreochromis niloticus (14 ± 6 mg et 1660 ± 8 mg, respectivement) ont été nourris avec3 aliments (A1, A2 et A3) formulés uniquement à base de sous-produits agricoles et un aliment industriel commercial contenant de la farine de poisson servant de témoin (At). Les alevins de 14 ± 6 mg et 1660 ± 8 mg ont été mis dans des bassins, à des densités respectives de 1667 et 500 ind/m 2. Deux essais expérimentaux ont été réalisés. Les résultats de l'élevage post-larvaire (14 ± 6 mg) montrent une variabilité inter-groupes non significative (p > 0,05). En revanche, une différence significative (p < 0,05) a été observée chez les juvéniles (1660 ± 8 mg), entre les lots soumis à l'aliment A1, puis A3 et At. Les poids moyens finaux atteints aux stades post-larvaire et juvénile ont été respectivement de 750 ± 180 et 5980 ± 1325 mg (A1), 730 ± 180 et 5340 ± 1264 mg (A2), 650 ± 50 et 4930 ± 1381 mg (A3), puis 680 ± 40 et 4880 ± 1152 mg (At). Comparés au témoin, l'analyse économique a montré une réduction des coûts des aliments tests et de production du kilogramme de juvéniles, respectivement à des taux de 30 %, et 30 à 49 %.
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