A Controlled Trial to Assess the Effect of Quinine, Chloroquine, Amodiaquine, and Artesunate on Loa loa Microfilaremia

Kamgno, Joseph; Nguipdop-Djomo, Patrick; Pion, S. D. S.; Thylefors, B; Boussinesq, Michel

doi:10.4269/ajtmh.2010.09-0573

Cited by 13 publications

(11 citation statements)

References 50 publications

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“…Repurposing attempts have been conducted with existing drugs with only limited success. The effect of several antimalarial drugs (quinine, chloroquine, amodiaquine and artesunate) was investigated on loiasis in a randomized, placebo-controlled approach in central Cameroon [ 20 ]. This study recorded no significant change in parasite loads in any of the treatment groups.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of in vitro culture systems for the maintenance of microfilariae and infective larvae of Loa loa

et al. 2018

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BackgroundSuitable and scalable in vitro culture conditions for parasite maintenance are needed to foster drug research for loiasis, one of the neglected tropical diseases which has attracted only limited attention over recent years, despite having important public health impacts. The present work aims to develop adequate in vitro culture systems for drug screening against both microfilariae (mf) and infective third-stage larvae (L3) of Loa loa.MethodsIn vitro culture conditions were evaluated by varying three basic culture media: Roswell Park Memorial Institute (RPMI-1640), Dulbecco’s modified Eagle’s medium (DMEM) and Iscove’s modified Dulbecco’s medium (IMDM); four sera/proteins: newborn calf serum (NCS), foetal bovine serum (FBS), bovine serum albumin (BSA) and the lipid-enriched BSA (AlbuMax® II, ALB); and co-culture with the Monkey Kidney Epithelial Cell line (LLC-MK2) as a feeder layer. The various culture systems were tested on both mf and L3, using survival (% motile), motility (T90 = mean duration (days) at which at least 90% of parasites were fully active) and moulting rates of L3 as the major criteria. The general linear model regression analysis was performed to assess the contribution of each variable on the viability of Loa loa L3 and microfilarie. All statistical tests were performed at 95% confidence interval.ResultsOf the three different media tested, DMEM and IMDM were the most suitable sustaining the maintenance of both L. loa L3 and mf. IMDM alone could sustain L3 for more than 5 days (T90 = 6.5 ± 1.1 day). Serum supplements and LLC-MK2 co-cultures significantly improved the survival of parasites in DMEM and IMDM. In co-cultures with LLC-MK2 cells, L. loa mf were maintained in each of the three basic media (T90 of 16.4–19.5 days) without any serum supplement. The most effective culture systems promoting significant moulting rate of L3 into L4 (at least 25%) with substantial maintenance time were: DMEM + BSA, DMEM + NCS, DMEM-AlbuMax®II, DMEM + FBS all in co-culture with LLC-MK2, and IMDM + BSA (1.5%), DMEM + FBS (10%) and DMEM + NCS (5%) without feeder cells. DMEM + 1% BSA in co-culture scored the highest moulting rate of 57 of 81 (70.37%). The factors that promoted L. loa mf viability included feeder cells (β = 0.490), both IMDM (β = 0.256) and DMEM (β = 0.198) media and the protein supplements NCS (β = 0.052) and FBS (β = 0.022); while for L. loa L3, in addition to feeder cells (β = 0.259) and both IMDM (β = 0.401) and DMEM (β = 0.385) media, the protein supplements BSA (β = 0.029) were found important in maintaining the worm motility.ConclusionsThe findings from this work display a range of culture requirements for the maintenance of Loa loa stages, which are suitable for developing an effective platform for drug screening.Electronic supplementary materialThe online version of this article (10.1186/s13071-018-2852-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Evaluation of in vitro culture systems for the maintenance of microfilariae and infective larvae of Loa loa

et al. 2018

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“…Our findings are consistent in general with expectations from previous in vitro and in vivo work and indicate that our culture system over a period of five days produces comparable and valid data. Among the agents used for comparison here, the anti-malarials ATS, CQ, AQ and QN have all been found inactive against L. loa mf in humans [ 48 ]. Except CQ, whose in vivo microfilaricidal activity has been proven against O. volvulus [ 49 ], agents that are known to be active against filariae and that were also active in our present studies are MQ [ 25 ] and imatinib, an anti-cancer compound recently added to the list of active filaricidal drugs [ 17 , 18 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity in the in vitro susceptibility of Loa loa microfilariae to drugs commonly used in parasitological infections

et al. 2018

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BackgroundCo-infection with loiasis remains a potential problem in control programs targeting filarial infections. The effects of many anti-parasitic drugs often administered to Loa loa infected people are not well documented. This study compared the in vitro activity of several of these drugs on the viability of L. loa microfilariae (mf).MethodsHuman strain L. loa mf were isolated from baboon blood using iso-osmotic Percoll gradient, and cultured in RPMI 1640/10% FBS with antimalarial drugs (mefloquine, amodiaquine, artesunate, chloroquine and quinine), anthelmintics (ivermectin, praziquantel, flubendazole and its reduced and hydrolyzed metabolites), two potential trypanocidal agents (fexinidazole and Scynexis-7158) and the anticancer drug imatinib. The drug concentrations used varied between 0.156 μg/ml and 10 μg/ml. Mf motility (CR50 = 50% immotility) and a metabolic viability assay (MTT) were used to assess the effects of these drugs on the parasites.ResultsMf in control cultures showed only a slight reduction in motility after 5 days of culture. Active inhibition of Loa loa motility was seen with mefloquine and amodiaquine (CR50 values of 3.87 and 4.05 μg/ml, respectively), immobilizing > 90% mf within the first 24 hours: mefloquine killed the mf after 24 hours of culture at concentrations ≥ 5 μg/ml. SCYX-7158 also induced a concentration-dependent reduction in mf motility, with > 50% reduction in mf motility seen after 5 days at 10 μg/ml. The anticancer drug imatinib reduced mf motility at 10 μg/ml from the first day of incubation to 55% by day 5, and the reduction in motility was concentration-dependent. Praziquantel and fexinidazole were inactive, and FLBZ and its metabolites, as well as ivermectin at concentrations > 5 μg/ml, had very minimal effects on mf motility over the first 4 days of culture.ConclusionsThe considerable action of the anti-malarial drugs mefloquine and amodiaquine on Loa mf in vitro highlights the possibility of repurposing the existing anti-infectious agents for the development of drugs against loiasis. The heterogeneity in the activity of anti-parasitic agents on Loa loa mf supports the need for further investigation using animal models of loiasis.Electronic supplementary materialThe online version of this article (10.1186/s13071-018-2799-3) contains supplementary material, which is available to authorized users.

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“…Differential efficacies of various antimalarial drugs (quinine, mefloquine, chloroquine, amodiaquine, quinacrine and primaquine) against filarial species have been reported. 11 These observations directed us to evaluate the possibility of antimalarial drugs consumption as a confounding variable for the absence of filarial infection. In the present report we enrolled both patients with SLE and healthy controls that had no history of clinical malaria in last 5 years.…”

Section: Sirmentioning

confidence: 99%

Absence of filarial infection in patients of systemic lupus erythematosus (SLE) in filarial endemic area: a possible protective role

Panda

Das

2014

Lupus

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A Controlled Trial to Assess the Effect of Quinine, Chloroquine, Amodiaquine, and Artesunate on Loa loa Microfilaremia

Cited by 13 publications

References 50 publications

Evaluation of in vitro culture systems for the maintenance of microfilariae and infective larvae of Loa loa

Evaluation of in vitro culture systems for the maintenance of microfilariae and infective larvae of Loa loa

Heterogeneity in the in vitro susceptibility of Loa loa microfilariae to drugs commonly used in parasitological infections

Absence of filarial infection in patients of systemic lupus erythematosus (SLE) in filarial endemic area: a possible protective role

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