Effect of Two or Six Doses 800 mg of Albendazole Every Two Months on Loa loa Microfilaraemia: A Double Blind, Randomized, Placebo-Controlled Trial

Kamgno, Joseph; Nguipdop-Djomo, Patrick; Gounoue, Racéline Kamkumo; Tejiokem, Mathurin Cyrille; Kuesel, Annette C.

doi:10.1371/journal.pntd.0004492

Cited by 34 publications

(26 citation statements)

References 38 publications

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“…Although high dose ALB (400 mg twice daily) for 3 weeks induced scrotal reactions in 11 of 15 men in one study (compared to zero of 13 DEC-treated men) [ 59 ], there is no evidence that adding single-dose ALB to IVM or DEC for LF MDA increases AEs [ 5 ]. In areas where LF is co-endemic with loiasis, semiannual ALB alone (together with integrated vector management) is recommended for LF MDA, because ALB can be safely given to persons with loiasis [ 60 , 61 ].…”

Section: Resultsmentioning

confidence: 99%

Adverse events following single dose treatment of lymphatic filariasis: Observations from a review of the literature

et al. 2018

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BackgroundWHO’s Global Programme to Eliminate Lymphatic Filariasis (LF) uses mass drug administration (MDA) of anthelmintic medications to interrupt LF transmission in endemic areas. Recently, a single dose combination of ivermectin (IVM), diethylcarbamazine (DEC), and albendazole (ALB) was shown to be markedly more effective than the standard two-drug regimens (DEC or IVM, plus ALB) for achieving long-term clearance of microfilaremia.Objective and methodsTo provide context for the results of a large-scale, international safety trial of MDA using triple drug therapy, we searched Ovid Medline for studies published from 1985–2017 that reported adverse events (AEs) following treatment of LF with IVM, DEC, ALB, or any combination of these medications. Studies that reported AE rates by treatment group were included.FindingsWe reviewed 162 published manuscripts, 55 of which met inclusion criteria. Among these, 34 were clinic or hospital-based clinical trials, and 21 were community-based studies. Reported AE rates varied widely. The median AE rate following DEC or IVM treatment was greater than 60% among microfilaremic participants and less than 10% in persons without microfilaremia. The most common AEs reported were fever, headache, myalgia or arthralgia, fatigue, and malaise.InterpretationMild to moderate systemic AEs related to death of microfilariae are common following LF treatment. Post-treatment AEs are transient and rarely severe or serious. Comparison of AE rates from different community studies is difficult due to inconsistent AE reporting, varied infection rates, and varied intensity of follow-up. A more uniform approach for assessing and reporting AEs in LF community treatment studies would be helpful.

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Section: Resultsmentioning

confidence: 99%

Adverse events following single dose treatment of lymphatic filariasis: Observations from a review of the literature

et al. 2018

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“…This study recorded no significant change in parasite loads in any of the treatment groups. Another study tested different intermittent doses of albendazole on Loa loa microfilaraemia, the reduction in mf load obtained was insufficient to prevent the risk of severe adverse reactions during ivermectin mass drug administration in loiasis co-endemic areas [ 21 ]. These observations demonstrated that repurposing of existing antiparasitic therapies may not be a suitable approach to develop drugs with satisfactory therapeutic window.…”

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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“…This group consisted of individuals tested positive with Loa loa microfilariaemia of greater than or equal to 30,000 mf/ml not taking part in mass drug administration programs. The subjects in this group were recruited previously for a study on the effects of albendazole of Loa loa microfilaraemia as described by Kamgno et al ., [ 45 ]. Serum samples from these Loa loa infected subjects were obtained from the Centre for research on filariasis and other tropical diseases, (CRFilMT), Yaoundé, Cameroon.…”

Section: Methodsmentioning

confidence: 99%

Prediction and validation of the structural features of Ov58GPCR, an immunogenic determinant of Onchocerca volvulus

et al. 2018

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Onchocerciasis is a severely debilitating yet neglected tropical disease (NTD) that creates social stigma, generates and perpetuates poverty, and leads ultimately in some cases to irreversible unilateral or bilateral blindness if untreated. Consequently, the disease is a major impediment to socioeconomic development. Many control programs have been launched for the disease with moderate successes achieved. This mitigated hit is partially due to the lingering need for reliable, non-invasive and easily applicable tools for mapping endemic regions and post-elimination surveillance. In this work, bioinformatics analyses combined with immunological assays were applied in a bid to develop potential tools for diagnosis and assessing the success of drug treatment programs. We report that (i) the O. volvulus antigen, Ov58GPCR is a G-protein coupled receptor (GPCR) conserved in related nematodes, (ii) synthetic peptides predicted to be in the extracellular domain (ECD) of Ov58GPCR are indeed immunogenic epitopes in actively-infected individuals, (iii) synthetic peptide cocktails discriminate between actively-infected individuals, treated individuals and healthy African controls, (iv) polyclonal antibodies against one of the peptides or against the bacterially-expressed ECD reacted specifically with the native antigen of O. volvulus total and surface extracts, (v) Ov58GPCR is transcribed in both larvae and adult parasite stages, (vi) IgG and IgE responses to the recombinant ECD decline with ivermectin treatment. All these findings suggest that the extracellular domain and synthetic peptides of Ov58GPCR, as well as the specific immune response generated could be harnessed in the context of disease diagnosis and surveillance.

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Effect of Two or Six Doses 800 mg of Albendazole Every Two Months on Loa loa Microfilaraemia: A Double Blind, Randomized, Placebo-Controlled Trial

Cited by 34 publications

References 38 publications

Adverse events following single dose treatment of lymphatic filariasis: Observations from a review of the literature

Adverse events following single dose treatment of lymphatic filariasis: Observations from a review of the literature

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

Prediction and validation of the structural features of Ov58GPCR, an immunogenic determinant of Onchocerca volvulus

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