Survival of Onchocerca volvulus in Nodules Implanted in Immunodeficient Rodents

Tv, Rajan; Fk, Nelson; Cupp, Eddie W.; Ld, Schultz; Dl, Greiner

doi:10.2307/3283709

Cited by 12 publications

(16 citation statements)

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“…Rajan et al previously described that exposed 'loops' of O. volvulus female worms embedded in onchocercomata could remain viable and contain developing mf for up to 20 wks post-implant in SCID mice [20], demonstrating the longterm feasibility of this approach. We speculate that the reduced biomass and less dense extra-cellular matrix of ochengi vs. volvulus onchocercomata may facilitate an increase in perfusion of host solutes, as well as our observations of neovascularization, to support protracted survival of implanted female macrofilariae.…”

Section: Discussionmentioning

confidence: 99%

“…Previous attempts to utilize inbred mouse strains, including lymphopenic strains, to establish Onchocerca macrofilarial infections from infectious stage (L3) larval inoculations, has thus far proven unsuccessful [19]. However, Rajan and colleagues demonstrated that O. volvulus female worm 'loops' , exposed from surrounding nodular encasement in excised nodules, could remain viable following implantation into Severe-Combined ImmunoDeficiency (SCID) mice [20].…”

Section: Introductionmentioning

confidence: 99%

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A murine macrofilaricide pre-clinical screening model for onchocerciasis and lymphatic filariasis

Halliday

Guimarães

Tyrer

et al. 2014

Parasites & Vectors

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Background: New drugs effective against adult filariae (macrofilaricides) would accelerate the elimination of lymphatic filariasis and onchocerciasis. Anti-Onchocerca drug development is hampered by the lack of a facile model. We postulated that SCID mice could be developed as a fmacrofilaricide screening model. Methods: The filaricides: albendazole (ABZ), diethylcarbamazine (DEC), flubendazole (FBZ), ivermectin (IVM) and the anti-Wolbachia macrofilaricide, minocycline (MIN) were tested in Brugia malayi (Bm)-parasitized BALB/c SCID mice vs vehicle control (VC). Responses were compared to BALB/c wild type (WT). Onchocerca ochengi male worms or onchocercomata were surgically implanted into BALB/c SCID, CB.17 SCID, BALB/c WT mice or Meriones gerbils. Survival was evaluated at 7-15 days. BALB/c SCID were tested to evaluate the responsiveness of pre-clinical macrofilaricides FBZ and rifapentine (RIFAP) against male Onchocerca. Results: WT and SCID responded with >95% efficacy following ABZ or DEC treatments against Bm larvae (P < 0.0001). IVM was partially filaricidal against Bm larvae in WT and SCID (WT; 39.8%, P = 0.0356 and SCID; 56.7%, P = 0.026). SCID responded similarly to WT following IVM treatment of microfilaraemias (WT; 79%, P = 0.0194. SCID; 76%, P = 0.0473). FBZ induced a total macrofilaricidal response against adult Bm in WT and SCID (WT; P = 0.0067, SCID; P = 0.0071). MIN induced a >90% reduction in Bm Wolbachia burdens (P < 0.0001) and a blockade of microfilarial release (P = 0.0215) in SCID. Male Onchocerca survival was significantly higher in SCID vs WT mice, but not gerbils, after +15 days (60% vs 22% vs 39% P = 0.0475). Onchocercoma implants had engrafted into host tissues, with evidence of neovascularisation, after +7 days and yielded viable macro/microfilariae ex vivo. FBZ induced a macrofilaricidal effect in Onchocerca male implanted SCID at +5 weeks (FBZ; 1.67% vs VC; 43.81%, P = 0.0089). Wolbachia loads within male Onchocerca were reduced by 99% in implanted SCID receiving RIFAP for +2 weeks.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A murine macrofilaricide pre-clinical screening model for onchocerciasis and lymphatic filariasis

Halliday

Guimarães

Tyrer

et al. 2014

Parasites & Vectors

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“…volvulus adult worms survived in scid mice for up to 20 weeks while still containing motile mf, indicating that adult worms have no nutritional requirements unique to a human host [47]. It was concluded that this protocol required scid mice because they are unable to reject the cotransplanted human tissue.…”

Section: Implantation Of Adult Worms Into Scid Micementioning

confidence: 99%

“…In the case of O. volvulus, worms were transplanted s.c. into C.B-17 scid mice without prior isolation from surrounding human host tissue, i.e. still located in the onchocercoma excised from patients 24 h earlier [47]. Furthermore, O. gutturosa adult worms were transplanted into CBA or Shasha mice with and without surrounding connective tissue capsules of their bovine hosts [48].…”

Section: Immune Responses To Adult Wormsmentioning

confidence: 99%

Immune responses to filarial infection in laboratory mice

Hörauf¹,

Fleischer²

1997

Med Microbiol Immunol

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Models of filarial infection in laboratory inbred mice are valuable tools for assessing the relevance of anti-filarial immune responses in protection against these parasites. However, laboratory mice are not permissive for those filarial species which are known to infect humans. Therefore, immunity to the different stages of these filariae, i.e. infective third stage larvae (L3), adults and microfilariae, has been analyzed separately, as a surrogate approach. Although much information has been gathered by analysis of immunity and intervention in particular immune responses in these experimental systems, interference of different stage-specific responses as well as modulation of filarial maturation by the immune system cannot be assessed. A newly established infection model of filariasis, namely infection of laboratory mice with Litomosoides sigmodontis, accommodates the full developmental cycle of the parasite and may overcome this deficiency. Although the disadvantage of this latter model is that it deals with a filaria which is not pathogenic to man, it is the only model in which immunity can be analyzed during maturation of infective larvae into adult worms, the period considered most important for vaccination studies.

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“…O. volvulus will grow only in the natural human host and a select group of nonhuman primates (1). Recently, in an attempt to establish infection in a murine system, human onchocercomata (skin nodules containing adult worms) were subcutaneously implanted into SCID mice (70). After up to 20 weeks in the mouse, onchocercomata contained both viable adult worms and microfilaria.…”

Section: Filariasismentioning

confidence: 99%