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[
Science,
1986]
Ivermectin, given to onchocerciasis patients as a single oral dose of 200 micrograms per kilogram of body weight, substantially reduced the uptake of Onchocerca volvulus microfilariae by Simulium yahense, an efficient black fly vector of the parasite in the tropical rain forests of West Africa. Three months after treatment, patients given ivermectin infected flies at a significantly lower rate than those who had received diethylcarbamazine or placebo, thereby reducing the number of developing larvae in the vector population. This diminished rate of infectiousness was also evident 6 months after treatment. These results strongly suggest that ivermectin could be effective in interrupting transmission of Onchocerca volvulus for epidemiologically important periods of time.
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Vieira JC, Dominguez A, Richards F, Cupp EW, Mendez-Galvan J, Sauerbrey M, Cupp MS, Eversole RR, Castro J, Guzman JR, Duke BO, Mackenzie CD
[
Am J Trop Med Hyg,
2004]
The objective of this study was to examine nodules from Mexico, Guatemala, and Ecuador collected over a one-year period (2001) to determine the effects of semi-annual ivermectin treatments on Onchocerca volvulus macrofilarial populations. Nodules were sectioned, stained with hematoxylin and eosin, and histologic findings were compared between countries and with historical data prior to the introduction of ivermectin into the region. Nodules from Ecuador had 10 times more dead or moribund worms than the historical control (66.6% versus 6.5%); nodules from patients from Mexico and Guatemala did not differ from the control. More than 80% of the female worms in each country were uninseminated and producing unfertilized oocytes. Nodules containing males differed in each country from the historical control (P < 0.0001), with presence of males ranging from 19.7% in Mexico to 13.6% in Ecuador versus 73% in the control. Nodules with females producing active microfilariae ranged from 7.8% (Mexico) to 2.7% (Ecuador) versus 60% in the historical control (P < 0.0001). Nodules from Ecuador and Mexico were significantly smaller in size than those from Guatemala or historical controls (P < 0.0005). These results depict a deteriorating condition of adult O. volvulus populations in Mexico, Guatemala and Ecuador, indicating that semi-annual ivermectin treatment of >/=6 years has had a profound effect on survival and reproduction of this species.
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[
Am J Trop Med Hyg,
2005]
A reanalysis of several published reports indicates that when community-wide biannual treatment disrupts transmission of new infection, a profound macrofilaricidal effect of ivermectin (Mectizan) occurs that is accelerated for individuals treated 4 times a year (4x/yr). The effect is particularly obvious on adult male worms and suggests that this gender is susceptible to repetitive treatment after transmission has been blocked or greatly reduced as a result of community treatment.
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[
Trop Med Parasitol,
1990]
The effects of co-culture with monkey kidney cells (LLCMK2), cell-conditioned medium and decreased atmospheric oxygen on the in vitro molting and viability of infective stage larvae (L3) of Onchocerca lienalis and O. volvulus were examined. O. lienalis L3 were cultured in an RPMI 1640-based medium in the presence of an LLCMK2 cell monolayer or in medium which had been conditioned for three days by cells. In paired experiments cell conditioned medium alone in 95% air/5% CO2 produced molting levels of 54 +/- 14% which increased to 67 +/- 20% in treatments cultured under decreased oxygen; this value equalled the level of molting of worms cocultured with LLCMK2 cells. Worm survival in the three environments was similar. In seven additional experiments using O. lienalis (n = 186), overall levels of 74 +/- 12 percent molting and 75 +/- 7% viability on days 21-33 were obtained. Worms increased in length from 503 +/- 50 mu as L3 to 638 +/- 74 mu as L4 on day 21 (p = 0.0001, n = 42-44). Ultrastructural comparison of an in vitro derived L4, (39 days in culture) vs a vector-derived L3 revealed fewer annulations and decreased osmiophilia on the epicuticle of the L4 while the hypodermis showed increased morphogenetic definition. O. volvulus molted at an average rate of 74% (n = 40) with a mean viability on day 28 of 95%. L3 increased in length from a mean of 635 +/- 50 mu to 775 +/- 45 mu as L4 on day 28 (p = 0.0001). Larvae of both species were cultured under these conditions for periods of time exceeding 100 days.
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[
Tropenmed Parasitol,
1980]
Two species of Nearctic black fly, Simulium decorum and S. pictipes, exhibit partial susceptibility to infection with the bovine parasite, Onchocerca lienalis, when inoculated intrathoracically with microfilariae. In addition, a proportion of S. decorum females will support the development of the human parasite, O. volvulus, to the third larvae stage. Infection rates with second- or third-stage larvae seven or more days after varied among geographic strains of S. decorum, ranging from 6.5% in a strain from northern New York State to 48.7% in a strain from Georgia. The average number of larvae per infected female ranged from 1.00 to 1.78 in the three strains examined. Partial susceptibility to O. lienalis was found to persist in colonized strains of s. decorum, and cryopreserved microfilariae of this parasite retained their infectivity. Seven or more days after inoculation with microfilariae of the Guatemalan strain of O. volvulus, 16.7% of the females of S. decorum harbored second- or third-stage larvae. Development of O. lienalis and O. volvulus proceeded normally in these black flies, and moderate increases in susceptibility rate and number of infective larvae were noted in response to increased microfilarial dosages.
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[
Am J Trop Med Hyg,
1991]
Adult Onchocerca volvulus worms, extracted from nodules of Guatemalans by collagenase digestion, were examined whole and by histological techniques. One group of persons received a single 150 micrograms/kg dose of ivermectin; two other groups (one with older and one with younger nodules) received four similar doses of ivermectin at 6-month intervals. For each group, there were comparable untreated controls. All nodules were removed six months after the last dose. After a single dose, the only significant difference from the controls was in the decreased proportion of female worms producing live microfilariae. After four doses, there were significant increases in the proportions of moribund/dead female worms and of live uninseminated females, when compared with the corresponding controls. There were also fewer male worms present, but this difference was not significant. Six months after the conclusion of the 4-dose regimen, the proportion of female worms producing live microfilariae was significantly lower than in the groups that had received a single dose.
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[
Am J Trop Med Hyg,
1990]
This paper assesses the effects on adult Onchocerca volvulus of monthly doses of ivermectin (150 micrograms/kg) given over 4, 8, and 12 months to patients in Guatemala. Nodules were removed 4 months after the last dose; the adult O. volvulus were extracted by collagenase digestion, studied by histological techniques, and compared with worms from untreated patients. Twelve monthly doses killed a proportion of the adult worms (12% of males and 22% of females), leaving the remainder relatively unaffected and the females slowly resuming embryogenesis. After 8 and 12 doses, a number of female worms had resumed embryogenesis in 1 genital tract only, and in 1 female a total degeneration of 1 ovary was seen. Ivermectin also led to a marked drop in the number of male worms in nodules. No serious adverse reactions occurred and the treatment was well accepted.
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[
Am J Trop Med Hyg,
1988]
Ivermectin was tested for possible prophylactic action against the third and fourth larval stages (L3 and L4) of Onchocerca volvulus inoculated into chimpanzees. The infective larvae (L3) were obtained from laboratory-raised black flies. Eighteen chimpanzees were inoculated, each with approximately 250 L3. Six were treated with ivermectin (200 micrograms/kg) on the day of inoculation, 6 were treated with ivermectin on day 28, and 6 were not treated. Monthly skin snips were taken for the next 30 months to detect patent infection. One of the chimpanzees treated with ivermectin on the day of infection developed a patent infection as did 4 of the 6 treated at day 28 and 4 of the 6 control animals. The results suggest that ivermectin may have a partial in vivo effect against the L3 of O. volvulus but has no effect against later larval stages of the parasite.
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[
PLoS Negl Trop Dis,
2019]
BACKGROUND: Onchocerciasis, or river blindness, has historically been an important cause of blindness, skin disease and economic disruption in Africa and the Americas. It is caused by the filarial parasite Onchocerca volvulus, which is transmitted by black flies in the genus Simulium. Over the past decade, several international programs have been formed to control, or more recently eliminate onchocerciasis, using mass drug administration (MDA) of ivermectin. However, in many areas of Africa (particularly those which are endemic for the eyeworm, Loa loa, or where vector densities are very high) ivermectin MDA alone will not be sufficient to achieve elimination. In these situations, additional interventions may be necessary. METHODOLOGY/PRINCIPAL FINDINGS: The Esperanza Window trap (EWT), a simple trap originally developed to replace human landing collections for entomological surveillance of O. volvulus transmission was optimized, resulting in a 17-fold improvement in trap performance. The optimized trap was tested in trials in schools and in agricultural fields to determine if it could reduce vector biting locally. The traps resulted in a 90% reduction in biting in the school setting. In the field setting, results varied. In one location, the traps reduced biting by roughly 50%, while in a separate trial, the traps did not significantly reduce the biting rate. Examination of the two settings suggested that trap placement may be critical to their success. CONCLUSIONS/SIGNIFICANCE: These results suggest that the optimized EWT might be capable of reducing local vector black fly biting in areas commonly frequented by residents. Together with other recently developed methods of community directed vector control, the traps may augment ivermectin MDA, bringing the goal of onchocerciasis elimination within reach in much of Africa.