Effect of a Single Standard Dose (150–200 μg/kg) of Ivermectin on<i>Loa loa</i>Microfilaremia: Systematic Review and Meta-analysis

Pion, Sébastien; Tchatchueng-Mbougua, Jules Brice; Chesnais, Cédric B.; Kamgno, Joseph; Gardon, Jacques; Chippaux, Jean-Philippe; Ranque, Stéphane; Ernould, Jean-Christophe; Garcia, André; Boussinesq, Michel

doi:10.1093/ofid/ofz019

Cited by 18 publications

(17 citation statements)

References 26 publications

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“…Ivermectin is an increasingly important drug for prevention and treatment of neglected tropical diseases and scabies [14][15][16]. Recently, the repurposing of ivermectin for the control of malaria has been identified as a public health priority due to its mosquitocidal activity [17].…”

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics of ivermectin for the treatment of scabies in Indigenous Australian children

et al. 2020

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Ivermectin is a broad-spectrum antiparasitic agent used for the treatment and control of neglected tropical diseases. In Australia, ivermectin is primarily used for scabies and is licensed in children aged ≥5 years weighing >15 kg. However, young children, aged <5 years, are particularly vulnerable to scabies and its secondary complications. Therefore, this study aimed to determine an appropriate ivermectin dose for children aged 2 to 4 years and weighing ≤15 kg. We conducted a prospective, pharmacokinetic study of ivermectin in Indigenous Australian children aged between 5 and 15 years and weighing >15 kg. Doses of 200 μg/kg rounded to the nearest whole or half 3 mg tablet were given to children with scabies and ivermectin concentrations determined at two time points after dosing. A population pharmacokinetic model was developed using non-linear mixed effects modelling. A separate covariate database of children aged 2 to 4 years and weighing <15 kg was used to generate 1000 virtual patients and simulate the dose required to achieve equivalent drug exposure in young children as those aged ≥5 years. Overall, 26 children who had 48 ivermectin concentrations determined were included, 11 (42%) were male, the median age was 10.9 years and median body weight 37.6 kg. The final model was a two-compartment model with first-order absorption and linear elimination. For simulated children aged 2 to 4 years, a dose of 3 mg in children weighing 10–15 kg produced similar drug exposures to those >5 years. The median simulated area under the concentration-time curve was 976 μg∙h/L. Using modelling, we have identified a dosing strategy for ivermectin in children aged 2 to 4 years and weighing less than 15 kg that can be prospectively evaluated for safety and efficacy.

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Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics of ivermectin for the treatment of scabies in Indigenous Australian children

et al. 2020

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“…The Yabassi Health District belongs to the Littoral CDTI project, and treatments with ivermectin have been initiated in that area since the years in the 2000s to fight onchocerciasis. Indeed, IVM is a macrocyclic lactone acting by killing almost 70–80% L. loa microfilariae within the first three days after a single dose of the drug, a total clearance being observed within 4–5 days in some individuals [ 27 , 28 ]. In addition to its principal effect (microfilaricidal), IVM also prevents for about three months the release of new microfilariae by adult female worms, so-called embryostatic effect.…”

Section: Discussionmentioning

confidence: 99%

Collateral Impact of Community-Directed Treatment with Ivermectin (CDTI) for Onchocerciasis on Parasitological Indicators of Loa loa Infection

Nana-Djeunga¹,

Lenou-Nanga²,

Donfo-Azafack³

et al. 2020

Pathogens

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Ivermectin (IVM) is a broad spectrum endectocide whose initial indication was onchocerciasis. Although loiasis is not among its indications, IVM also exhibits antiparasitic activity against Loa loa. IVM-based preventive chemotherapies (PCs), so-called community-directed treatment with ivermectin (CDTI), have led to the interruption of transmission of onchocerciasis in some foci. A cross-sectional study was conducted in the Yabassi Health District where CDTI have been implemented since 20 years to fight onchocerciasis. All volunteers aged ≥ 5 years underwent daytime calibrated thick blood smears to search for L. loa microfilariae (mf). The prevalence of loiasis was 3.7% (95% CI: 2.2–6.2), significantly lower than its baseline prevalence (12.4%; 95% CI: 10.1–15.2; Chi-Square = 21.4; df = 1; p < 0.0001). Similarly, the microfilarial density was significantly low (mean = 1.8 mf/mL; SD = 13.6; max = 73,600) compared to baseline microfilarial density (mean = 839.3 mf/mL; SD = 6447.1; max = 130,840; Wilcoxon W = 179,904.5; p < 0.0001). This study revealed that the endemicity level of loiasis was significantly low compared to its baseline value, indicating a significant impact of IVM-based PC on this filarial disease. However, transmission is still ongoing, and heavily infected individuals are still found in communities, supporting why some individuals are still experiencing severe adverse events despite > 2 decades of CDTI in this Health District.

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“…The Yabassi Health District belongs to the Littoral CDTI project, and treatments with ivermectin have been initiated in that area since the years 2000s to ght onchocerciasis. Indeed, IVM is a macrocyclic lactone acting by killing almost 70-80% L. loa micro lariae within the rst three days after a single dose of the drug, a total clearance being observed within 4-5 days in some individuals [29][30]. In addition to its principal effect (micro laricidal), IVM also prevents for about three months the release of new micro lariae by adult female worms, so-called embryostatic effect.…”

Section: Discussionmentioning

confidence: 99%

Collateral impact of community-directed treatment with ivermectin (CDTI) for onchocerciasis on parasitological indicators of Loa loa infection

Djeunga¹,

Lenou-Nanga²,

Donfo-Azafack³

et al. 2020

Preprint

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Background Ivermectin (IVM) is a broad spectrum endectocide whose initial indication was onchocerciasis. IVM-based preventive chemotherapies (PC), so-called Community-Directed Treatment with Ivermectin (CDTI), have led to the interruption of transmission of onchocerciasis in some foci. Although loiasis is not among its indications, IVM also exhibits antiparasitic activity against Loa loa. Because of the geographic overlap of onchocerciasis and loiasis in Central Africa, one would have expected similar trend for loiasis in co-endemic settings. Surprisingly, a recent study revealed that L. loa entomological indices remained almost unchanged after 13 years of CDTI to fight onchocerciasis. This study then aimed to assess whether parasitological indicators of L. loa infection follow the same trends than the previously described entomological indices. A cross-sectional study was conducted in six communities of the Yabassi Health District where CDTI have been implemented since ~ 20 years to fight onchocerciasis. All volunteers aged ≥ 5 years underwent daytime calibrated thick blood smears to search for L. loa microfilariae (mf), then prevalence and intensity of infection were compared to baseline data. Results A total of 376 individuals (55.9% female), aged 5 to 89 years old, were enrolled in this study. The prevalence of loiasis was 3.7% (95% CI: 2.2–6.2), significantly lower than its baseline (12.4%; 95% CI: 10.1–15.2) (Chi-Square = 21.4; df = 1; p < 0.0001). Similarly, the microfilarial density was significantly low (Mean = 1.8 mf/mL; SD = 13.6; max = 73,600) compared to baseline (Mean = 839.3 mf/mL; SD = 6447.1; max = 130,840) (Wilcoxon W = 179904.5; p < 0.0001). Conclusions This study revealed that the prevalence and intensity of L. loa infection were significantly low compared to their baselines, indicating a significant impact of IVM-based PC on this filarial disease. However, transmission is still ongoing, and heavily infected individuals are still found in communities, supporting why some individuals are still experiencing severe adverse events despite > 2 decades of CDTI in this Health District.

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Effect of a Single Standard Dose (150–200 μg/kg) of Ivermectin onLoa loaMicrofilaremia: Systematic Review and Meta-analysis

Cited by 18 publications

References 26 publications

Population pharmacokinetics of ivermectin for the treatment of scabies in Indigenous Australian children

Population pharmacokinetics of ivermectin for the treatment of scabies in Indigenous Australian children

Collateral Impact of Community-Directed Treatment with Ivermectin (CDTI) for Onchocerciasis on Parasitological Indicators of Loa loa Infection

Collateral impact of community-directed treatment with ivermectin (CDTI) for onchocerciasis on parasitological indicators of Loa loa infection

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