Animal models—<i>Onchocerca ochengi</i>and the development of chemotherapeutic and chemoprophylactic agents for onchocerciasis

Trees, A. J.; Wood, V L; Bronsvoort, Mark; Renz, Alfons; Tanya, Vincent N.

doi:10.1080/00034983.1998.11813389

Cited by 15 publications

(8 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This species is phylogenetically closely related to O. volvulus for which it provides an excellent analogue [17] and was formerly adopted by the World Health Organisation (WHO) tertiary drug screening system for macrofilaricides until 2000. Previous studies have indicated both its practical merits and its predictive value [18-20]. …”

Section: Introductionmentioning

confidence: 99%

Repeated high doses of avermectins cause prolonged sterilisation, but do not kill, Onchocerca ochengiadult worms in African cattle

et al. 2005

View full text Add to dashboard Cite

BackgroundIvermectin (Mectizan™, Merck and CO. Inc.) is being widely used in the control of human onchocerciasis (Onchoverca volvulus) because of its potent effect on microfilariae. Human studies have suggested that, at the standard dose of 150 μg/kg an annual treatment schedule of ivermectin reversibly interferes with female worm fertility but is not macrofilaricidal. Because of the importance of determining whether ivermectin could be macrofilaricidal, the efficacy of high and prolonged doses of ivermectin and a related avermectin, doramectin, were investigated in cattle infected with O. ochengi.MethodsDrugs with potential macrofilaricidal activity, were screened for the treatment of human onchocerciasis, using natural infections of O. ochengi in African cattle. Three groups of 3 cows were either treated at monthly intervals (7 treatments) with ivermectin (Ivomec®, Merck and Co. Inc.) at 500 μg/kg or doramectin (Dectamax®, Pfizer) at 500 μg/kg or not treated as controls. Intradermal nodules were removed at 6 monthly intervals and adult worms were examined for signs of drug activity.ResultsThere was no significant decline in nodule diameter, the motility of male and female worms, nor in male and female viability as determined by the ability to reduce tetrazolium, compared with controls, at any time up to 24 months from the start of treatments (mpt). Embryogenesis, however, was abrogated by treatment, which was seen as an accumulation of dead and dying intra-uterine microfilariae (mf) persisting for up to 18 mpt. Skin mf densities in treated animals had fallen to zero by <3 mpt, but by 18 mpt small numbers of mf were found in the skin of some treated animals and a few female worms were starting to produce multi-cellular embryonic stages. Follow-up of the doramectin treated group at 36 mpt showed that mf densities had still only regained a small proportion of their pre-treatment levels.ConclusionThese results have important implications for onchocerciasis control in the field. They suggest that ivermectin given at repeated high does may sterilise O. volvulus female worms for prolonged periods but is unlikely to kill them. This supports the view that control programmes may need to continue treatments with ivermectin for a period of decades and highlights the need to urgently identify new marcofiliaricidal compounds.

show abstract

Section: Introductionmentioning

confidence: 99%

Repeated high doses of avermectins cause prolonged sterilisation, but do not kill, Onchocerca ochengiadult worms in African cattle

et al. 2005

View full text Add to dashboard Cite

show abstract

“…In recent years animal filarial parasites infecting cattle in savanna areas of Africa have attracted research interest [1,16,18,[20][21][22]. This trend has been largely attributed to the demonstration that the bovine Onchocerca species, O. ochengi Bwangamoi, 1969 is so far the best animal model available for studies on drug screens against human onchocerciasis [16].…”

Section: Introductionmentioning

confidence: 99%

Onchocerca ochengitransmission dynamics and the correlation ofO. ochengimicrofilaria density in cattle with the transmission potential

2000

View full text Add to dashboard Cite

-The intensity of natural transmission of Onchocerca ochengi and Onchocerca volvulusby anthropo-boophilic Simulium damnosum s.l. was studied longitudinally in two cattle watering sites of a cattle ranch within a predominantly cattle populated area of the Guinea savanna of Cameroon and related to cattle O. ochengi skin microfilaria abundance. During the 12 months study period, a total of 4 696 flies was individually dissected to examine the monthly transmission potential (MTP) of O. ochengi and O. volvulus. The estimated Simulium damnosum s.l. annual biting rates (ABR) on human baits were 47 529 flies at the bank of the Vina "du sud" river. The ABR at the lake, which was situated at about 2 km upland from the perennial river, was 8 579. The monthly parous rate was highly correlated with monthly biting rate. The annual transmission potentials (ATP) of O. ochengi were calculated to be 7 732 and 1 669 at the riverbank and the lake, respectively. Transmission occurred mainly in the dry season, peaking in the months of January to mid-March when dermal microfilaria density in the animals was also the highest. The O. ochengi microfilaria uptake by the fly vectors was host microfilaria density-dependent. The MTP of O. ochengi was positively correlated with dermal microfilaria density. The mean number of microfilariae per fly taken up during a blood meal was high during the dry season as was the mean number of infective larvae per fly but declined significantly with the onset of the early rains. A similar seasonality of transmission was also observed for O. volvulus that was concurrently transmitted by the same vector flies, but its ATP was comparatively much lower: 1 332 infective larvae per man per year at the riverbank and 107 around the lake. The population dynamics of cattle microfilariae therefore plays an important role in the regulation of O. ochengi transmission.transmission / Onchocerca ochengi / Onchocerca volvulus / microfilariae density / Simulium damnosum s.l. Vet. Res. 31 (2000) 611-621 611

show abstract

“…1 ). For the past two decades, O. ochengi has been exploited in its natural host as an advanced screen for drug ( 34 ) and vaccine development ( 35 ), and has also revealed fundamental insights into the symbiosis between filariae and Wolbachia ( 36 , 37 ). We show that the proteome of O. ochengi exhibits both qualitative and quantitative dynamic changes during development and that the protein families undergoing regulation have almost identical orthologs in O. volvulus .…”

mentioning

confidence: 99%

Stage-specific Proteomes from Onchocerca ochengi, Sister Species of the Human River Blindness Parasite, Uncover Adaptations to a Nodular Lifestyle

Armstrong

Xia

Bah

et al. 2016

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Despite 40 years of control efforts, onchocerciasis (river blindness) remains one of the most important neglected tropical diseases, with 17 million people affected. The etiological agent, Onchocerca volvulus, is a filarial nematode with a complex lifecycle involving several distinct stages in the definitive host and blackfly vector. The challenges of obtaining sufficient material have prevented high-throughput studies and the development of novel strategies for disease control and diagnosis. Here, we utilize the closest relative of O. volvulus, the bovine parasite Onchocerca ochengi, to compare stage-specific proteomes and host-parasite interactions within the secretome. We identified a total of 4260 unique O. ochengi proteins from adult males and females, infective larvae, intrauterine microfilariae, and fluid from intradermal nodules. In addition, 135 proteins were detected from the obligate Wolbachia symbiont. Observed protein families that were enriched in all whole body extracts relative to the complete search database included immunoglobulin-domain proteins, whereas redox and detoxification enzymes and proteins involved in intracellular transport displayed stage-specific overrepresentation. Unexpectedly, the larval stages exhibited enrichment for several mitochondrial-related protein families, including members of peptidase family M16 and proteins which mediate mitochondrial fission and fusion. Quantification of proteins across the lifecycle using the Hi-3 approach supported these qualitative analyses. In nodule fluid, we identified 94 O. ochengi secreted proteins, including homologs of transforming growth factor-β and a second member of a novel 6-ShK toxin domain family, which was originally described from a model filarial nematode (Litomosoides sigmodontis). Strikingly, the 498 bovine proteins identified in nodule fluid were strongly dominated by antimicrobial proteins, especially cathelicidins. This first high-throughput analysis of an Onchocerca spp. proteome across the lifecycle highlights its profound complexity and emphasizes the extremely close relationship between O. ochengi and O. volvulus. The insights presented here provide new candidates for vaccine development, drug targeting and diagnostic biomarkers.

show abstract

Animal models—Onchocerca ochengiand the development of chemotherapeutic and chemoprophylactic agents for onchocerciasis

Cited by 15 publications

References 11 publications

Repeated high doses of avermectins cause prolonged sterilisation, but do not kill, Onchocerca ochengiadult worms in African cattle

Repeated high doses of avermectins cause prolonged sterilisation, but do not kill, Onchocerca ochengiadult worms in African cattle

Onchocerca ochengitransmission dynamics and the correlation ofO. ochengimicrofilaria density in cattle with the transmission potential

Stage-specific Proteomes from Onchocerca ochengi, Sister Species of the Human River Blindness Parasite, Uncover Adaptations to a Nodular Lifestyle

Contact Info

Product

Resources

About