Prolonged clearance of microfilaraemia in patients with bancroftian filariasis after multiple high doses of ivermectin or diethylcarbamazine

Ismail, M. M.; Weil, Gary J.; Jayasinghe, Kosala Saroj Amarasiri; Premaratne, U. N.; Abeyewickreme, W.; Rajaratnam, H.N.; Sheriff, M H Rezvi; Perera, Chiara; Dissanaike, A. S.

doi:10.1016/s0035-9203(96)90437-x

Cited by 49 publications

(27 citation statements)

References 16 publications

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“…Previous studies have shown that filarial antigen levels decrease by ∼ 50% after single-dose DEC treatment, 18,25,26 and a 61% decrease was observed in the present study. Previous studies have also reported that filarial antigen tests usually remain positive after single-dose DEC treatment, and this was also true for the majority of subjects in the present study, including some who completely cleared MF after treatment.…”

Section: Discussionsupporting

confidence: 75%

The impact of single-dose diethylcarbamazine treatment of bancroftian filariasis in a low-endemicity setting in Egypt.

Ramzy¹,

El-Setouhy²,

Helmy³

et al. 2002

The American Journal of Tropical Medicine and Hygiene

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Abstract. This study was designed to evaluate the effect of a single dose of diethylcarbamazine (DEC, 6 mg/kg) on Wuchereria bancrofti infections in a low-endemicity setting in Egypt (microfilaremia, or MF, 3.7%, median MF 34/mL). Subjects with MF or filarial antigenemia were treated and restudied 1 year later. Treatment with DEC dramatically reduced blood MF counts, with clearance in 69% of subjects. Treatment also reduced filarial antigen levels, but low clearance rates suggest that some adult worms survived treatment in most patients. Mass treatment was administered in one village; 27 months later, MF prevalence had decreased 84% (from 4.9% to 0.8%). These results show that singledose DEC treatment can have a major effect on MF prevalence rates and levels in low-endemicity settings. Although the World Health Organization advocates repeated multidrug regimens for filariasis elimination, mass treatment with DEC alone may be sufficient to interrupt transmission in areas with low infection intensities and prevalence rates.

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Section: Discussionsupporting

confidence: 75%

The impact of single-dose diethylcarbamazine treatment of bancroftian filariasis in a low-endemicity setting in Egypt.

Ramzy¹,

El-Setouhy²,

Helmy³

et al. 2002

The American Journal of Tropical Medicine and Hygiene

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“…lymphatic filariasis, onchocerciasis, loaisis, ascariasis, trichuriasis, hookworm and lice), in more than 20 clinical trials in ten countries, including India [42], Cameroon [23], Ghana [43], Gabon [44], Sri Lanka [45–47], Mali [48], Papua New Guinea [49, 50], French Polynesia [51–58], Brazil [59–62], Haiti [63, 64], and France [65]. Repeated ivermectin administration at doses of 400 µg/kg was safe in two trials in adults who were treated every two weeks for 12 weeks in Sri Lanka [45] and Brazil [61]. The ivermectin dose of 400 µg/kg was deemed safe enough to perform several rounds of MDA to thousands of people in India [42], Cameroon [23], Papua New Guinea [49], and French Polynesia [56, 57] with minimal adverse events reported.…”

Section: Discussionmentioning

confidence: 99%

Ivermectin susceptibility and sporontocidal effect in Greater Mekong Subregion Anopheles

Kobylinski

Ubalee

Ponlawat

et al. 2017

Malar J

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BackgroundNovel vector control methods that can directly target outdoor malaria transmission are urgently needed in the Greater Mekong Subregion (GMS) to accelerate malaria elimination and artemisinin resistance containment efforts. Ivermectin mass drug administration (MDA) to humans has been shown to effectively kill wild Anopheles and suppress malaria transmission in West Africa. Preliminary laboratory investigations were performed to determine ivermectin susceptibility and sporontocidal effect in GMS Anopheles malaria vectors coupled with pharmacokinetic models of ivermectin at escalating doses.MethodsA population-based pharmacokinetic model of ivermectin was developed using pre-existing data from a clinical trial conducted in Thai volunteers at the 200 µg/kg dose. To assess ivermectin susceptibility, various concentrations of ivermectin compound were mixed in human blood meals and blood-fed to Anopheles dirus, Anopheles minimus, Anopheles sawadwongporni, and Anopheles campestris. Mosquito survival was monitored daily for 7 days and a non-linear mixed effects model with probit analyses was used to calculate concentrations of ivermectin that killed 50% (LC50) of mosquitoes for each species. Blood samples were collected from Plasmodium vivax positive patients and offered to mosquitoes with or without ivermectin at the ivermectin LC25 or LC5 for An. dirus and An. minimus.ResultsThe GMS Anopheles displayed a range of susceptibility to ivermectin with species listed from most to least susceptible being An. minimus (LC50 = 16.3 ng/ml) > An. campestris (LC50 = 26.4 ng/ml) = An. sawadwongporni (LC50 = 26.9 ng/ml) > An. dirus (LC50 = 55.6 ng/ml). Mosquito survivorship results, the pharmacokinetic model, and extensive safety data indicated that ivermectin 400 µg/kg is the ideal minimal dose for MDA in the GMS for malaria parasite transmission control. Ivermectin compound was sporontocidal to P. vivax in both An. dirus and An. minimus at the LC25 and LC5 concentrations.ConclusionsIvermectin is lethal to dominant GMS Anopheles malaria vectors and inhibits sporogony of P. vivax at safe human relevant concentrations. The data suggest that ivermectin MDA has potential in the GMS as a vector and transmission blocking control tool to aid malaria elimination efforts.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-1923-8) contains supplementary material, which is available to authorized users.

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“…Vaccination against larval infection is possible, as dose-dependent responses have been demonstrated using killed and irradiated microfilarial and larval vaccines of several filarial worm species, and abbreviated larval infections with D. immitis [67, 90, 92, 108], O. volvulus [109], Loa loa [110], B. malayi [71, 111] and W. bancrofti [112]. Additionally, concurrent administration of the immunostimulant Freund’s complete adjuvant (FCA) with an abbreviated larval infection elicited a stronger protective immune response than an abbreviated infection without FCA, or an irradiated infection alone [92].…”

Section: Administration To Filarial Wormsmentioning

confidence: 99%

“…However, repeated doses at sufficient intervals with either live or killed vaccines elicit a memory response, which results in a higher antibody titer and more effective immune protection [93, 109, 110, 112]. …”

Section: Administration To Filarial Wormsmentioning

confidence: 99%

Examining the role of macrolides and host immunity in combatting filarial parasites

Carithers

2017

Parasites Vectors

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Macrocyclic lactones (MLs), specifically the avermectins and milbemycins, are known for their effectiveness against a broad spectrum of disease-causing nematodes and arthropods in humans and animals. In most nematodes, drugs in this class induce paralysis, resulting in starvation, impaired ability to remain associated with their anatomical environment, and death of all life stages. Initially, this was also thought to be the ML mode of action against filarial nematodes, but researchers have not been able to validate these characteristic effects of immobilization/starvation of MLs in vitro, even at higher doses than are possible in vivo. Relatively recently, ML receptor sites exclusively located proximate to the excretory-secretory (ES) apparatus were identified in Brugia malayi microfilaria and an ML-induced suppression of secretory protein release by B. malayi microfilariae was demonstrated in vitro. It is hypothesized here that suppression of these ES proteins prevents the filarial worm from interfering with the host’s complement cascade, reducing the ability of the parasite to evade the immune system. Live microfilariae and/or larvae, thus exposed, are attacked and presented to the host’s innate immune mechanisms and are ultimately killed by the immune response, not the ML drug. These live, exposed filarial worms stimulate development of innate, cellular and humoral immune responses that when properly stimulated, are capable of clearing all larvae or microfilariae present in the host, regardless of their individual sensitivity to MLs. Additional research in this area can be expected to improve our understanding of the relationships among filarial worms, MLs, and the host immune system, which likely would have implications in filarial disease management in humans and animals.

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Prolonged clearance of microfilaraemia in patients with bancroftian filariasis after multiple high doses of ivermectin or diethylcarbamazine

Cited by 49 publications

References 16 publications

The impact of single-dose diethylcarbamazine treatment of bancroftian filariasis in a low-endemicity setting in Egypt.

The impact of single-dose diethylcarbamazine treatment of bancroftian filariasis in a low-endemicity setting in Egypt.

Ivermectin susceptibility and sporontocidal effect in Greater Mekong Subregion Anopheles

Examining the role of macrolides and host immunity in combatting filarial parasites

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