Renz A (1987) Ann Trop Med Parasitol "Studies on the dynamics of transmission of onchocerciasis in a Sudan-savanna area of North Cameroon III. Infection rates of the Simulium vectors and Onchocerca volvulus transmission potentials."

Renz A

[Ann Trop Med Parasitol, 1987]

Populations of Simulium damnosum s.str. and S. sirbanum were examined for infections with filarial parasites during three years in the areas of Tchollire and Touboro, at sites at different distances from Simulium breeding rivers, and in relation to villages with different endemicities of onchocerciasis. A total of 60,353 flies from 23 fly-catching sites were dissected. The overall infection rate was low, 11.8% of 35,357 parous flies dissected. 1681 flies (4.8% of the total parous) contained 3557 infective larvae, 68.8% of which were morphologically indistinguishable from Onchocerca volvulus and 31.2% were infective 'Type D' larvae of non-human origin, indicating a high degree of zoophily of the fly populations. It was estimated that only 20-40% of all bloodmeals were taken from man. The majority (54%) of all infective O. volvulus larvae were found in the heads of the flies, the remainder being in the thorax (34%) and abdomen (12%). Only 54% of the O. volvulus infective larvae left their vectors during a bloodmeal which, however, was not completed in most cases. During the rainy season infection rates with O. volvulus infective larvae were 3.5% of the total parous flies, as compared with 1.8% during the dry season. The average number of infective larvae of O. volvulus per infective fly was 2.6 and 2.2 during the rainy and dry seasons respectively. These variations in the vectorial efficiency of the fly populations, as well as variations from one site to another, could be explained by different survival rates and man-biting habits of the various vector populations during the dry and rainy seasons and in different regions, rather than by different endemic profiles of onchocerciasis in the human population. The intensity of transmission varied seasonally and was highest (1609 to 3076 infective larvae/man/year) near the main breeding sites, where transmission was almost perennial. At distances of more than 3 km from the river transmission was mainly restricted to the rainy season and the Annual Transmission Potential was below 200, whereas low to zero levels of transmission were measured inside villages more than 3 km distant from the river. The coefficient of variation of the Annual Transmission Potentials over the three years of studies was from 31% to 192% of the mean, being higher that the variations in the corresponding levels of the biting rates, due to the low numbers of infective flies dissected at sites with low transmission.(ABSTRACT TRUNCATED AT 400 WORDS)

Renz A et al. (1983) Trans R Soc Trop Med Hyg "The distribution of the microfilariae of Onchocerca volvulus in the different body regions in relation to the attacking behaviour of Simulium damnosum s.l. in the Sudan savanna of northern Cameroon."

Wenk P, Renz A

[Trans R Soc Trop Med Hyg, 1983]

Densities of Onchocerca volvulus microfilariae in four volunteers with low to moderate infections were estimated at five body sites by paired skin snips. The landing of Simulium damnosum s.1. females on the body of these volunteers was recorded during 12 hours for six days. Most flies fed at the ankles (53% and 51%) and calves (28% and 27% respectively) in both the standing and sitting positions. The density of microfilariae in the skin was highest in the pelvic region (24.1 mf/mg) and relatively low in the calf (14.8 mf/mg) and ankle (1.0 mf/mg) regions. From the biting rate (females/body part) and the microfilarial density (mf/mg) a transmission index was calculated for the different body regions. This was highest for the calves showing that this part of the leg, if unclothed, accounts for the highest rate of contact (50 to 60% of total) between vector and parasite.

Eichner M et al. (1990) Trop Med Parasitol "Differential length of Onchocerca volvulus infective larvae from the Cameroon rain forest and savanna."

Renz A, Eichner M

[Trop Med Parasitol, 1990]

Infective larvae from the savanna strain of Onchocerca volvulus are significantly longer (662.6 +/- 66.8 microns; n = 99) than those from the forest strain (624.2 +/- 62.0 microns; n = 236). The length of the infective larvae is not influenced by the size, species or age post infectionem (pi) of the Simulium damnosum s. l. vectors nor by their localization in the fly's head, thorax or abdomen, the worm load per fly or the thoracic volume per larva. However, the lengths of infective larvae within one individual fly have a conspiciously low variance.

Harnett W et al. (1989) Mol Biochem Parasitol "An oligonucleotide probe specific for Onchocerca volvulus."

Harnett W, Chambers AE, Renz A, Parkhouse RM

[Mol Biochem Parasitol, 1989]

A genomic DNA library of a Liberian strain of Onchocerca volvulus was prepared in the vector bacteriophage lambda gt10. The library was differentially screened by hybridisation with radiolabelled total DNA from the homologous parasite, two heterologous Onchocerca parasites (Onchocerca gibsoni and Onchocerca gutturosa) and human liver cells. A clone (C1A1) was isolated whose binding to O. volvulus DNA was at least 50 times stronger than to the other parasite DNA samples. No binding was observed with human DNA. The insert of C1A1 was subcloned into the filamentous phage vector M13 mp18 and sequenced. Two oligonucleotides, each corresponding to a unique region of 60 nucleotides (out of a total of 154) were synthesised and examined for hybridisation with three different geographical isolates of O. volvulus (including forest and savannah strains) and six other Onchocerca spp. One of the oligonucleotides (C1A1-2) was found to hybridise to the three O. volvulus isolates with an intensity in the region of 300 times greater than to any other Onchocerca spp. Since the other species include the two which may be most closely related to O. volvulus, i.e., O. gibsoni and Onchocerca ochengi, it is concluded that C1A1-2 is likely to represent a truly species-specific probe.

Hildebrandt JC et al. (2014) Vet Parasitol "Reproductive biology of Onchocerca ochengi, a nodule forming filarial nematode in zebu cattle."

Streit A, Eisenbarth A, Renz A, Hildebrandt JC

[Vet Parasitol, 2014]

Onchocerca ochengi is a nodule-forming filarial nematode parasite of cattle in tropical Africa and closely related to the human pathogen Onchocerca volvulus. The adult worms reside in intradermal nodules. While females are sedentary, males may move between nodules. The first stage larvae (microfilariae) disperse in the skin of the host waiting to be taken up by the intermediate host. The density of microfilariae in the skin is largely independent of the number of adult worms present indicating some form of density dependent control. Recently, Onchocerca sp. Siisa, a form of Onchocerca distinguishable from O. ochengi by mitochondrial DNA sequences but not by morphology, was described to occur in cattle. This raised the question if Onchocerca sp. Siisa represents a different mitochondrial clade of O. ochengi or a new species. In order to study the reproductive biology and to understand this self-control of the off-spring population we systematically analyzed all Onchocerca nodules from the skin of one zebu cow and we examined a sample of microfilariae from a skin biopsy. We identified 87 O. ochengi females and 146 males. 56 (64.4%) of the females contained developing embryos. In order to assign the progeny to their respective parents we determined the genotypes at six nuclear and two mitochondrial molecular genetic markers in the adult worms, in a fraction of the progeny present in the uteri of the females and in the skin microfilariae. The 121 skin microfilariae we analyzed originated from at least 17 different mothers, which contributed rather differently to the total. Forty-five larvae (37.2%) were the progeny of a single female. Of the adult worms 16.7% were of the type Onchocerca sp. Siisa. These worms appeared to interbreed freely with the rest of the O. ochengi population and therefore belong to the same species.

Hildebrandt JC et al. (2012) Parasitol Res "Single worm genotyping demonstrates that Onchocerca ochengi females simultaneously produce progeny sired by different males."

Renz A, Eisenbarth A, Hildebrandt JC, Streit A

[Parasitol Res, 2012]

Onchocerca ochengi is a filarial nematode parasite of African cattle and most closely related to Onchocerca volvulus, the causing agent of river blindness. O. ochengi females induce the formation of a nodule in the dermis of the host, in which they remain sedentary in very close association with the host's tissue. Males, which do not adhere to the host's tissue, are also found within the nodules at an average number of about one male per nodule. Young O. ochengi females tend to avoid the immediate proximity of existing nodules. Therefore, O. ochengi nodules are dispersed in the ventral inguinal skin at considerable distances from each other. It has been speculated that males avoid the risk of leaving a female once they have found one and remain in the nodule as territorial males rendering the reproductive strategy of O. ochengi essentially monogamous. We developed a protocol that allows reliable PCR amplification of single copy loci from different developmental stages of O. ochengi including embryos and microfilariae. From 32 O. ochengi nodules, we genotyped the female worms and the 67 adult male worms, found in these nodules, together with a fraction of the progeny from within the uteri of females. In 18 of 32 gravid females progeny derived from multiple males were found. In five nodules, the males isolated from the same nodule as the female were not sufficient to explain the genotypes of the entire progeny. We conclude that frequently O. ochengi females simultaneously produce progeny sired by different males and that most but not all males are still present in the nodule when their offspring is ready to hatch.

Achukwi MD et al. (2007) Parasite Immunol "Successful vaccination against Onchocerca ochengi infestation in cattle using live Onchocerca volvulus infective larvae."

Enyong P, Renz A, Harnett W, Achukwi MD

[Parasite Immunol, 2007]

Epidemiological evidence has led to the hypothesis that the concurrent and predominant transmission of Onchocerca ochengi by Simulium damnosum s.l. in sub-Saharan Africa could lead to the protection of humans against onchocerciasis caused by Onchocerca volvulus (zooprophylaxis). To gain support for this hypothesis, we investigated whether exposure to O. volvulus could protect cattle from O. ochengi. Gudali calves were vaccinated with live O. volvulus-infective larvae and subsequently challenged with O. ochengi-infective larvae whilst raised in a fly-proof house. Post-challenge adult parasite and microfilaria development, IgG1 and lgG2 subclass antibodies response to Ov10/Ov11 recombinant Onchocerca antigens, and peripheral blood lymphocyte proliferative responses to O. ochengi crude antigens were studied over a 1-year period. The vaccinated-challenged animals had 83-87% less adult O. ochengi parasites than non-vaccinated-challenged animals. IgG1 and lgG2 antibodies to Ov10/Ov11 recombinant Onchocerca antigens were invoked by non-vaccinated-challenged animals but not by most (80%) of the vaccinated-challenged animals. These findings support the idea of cross-protection (zooprophylaxis) due to inoculation of humans with O. ochengi-infective larvae under natural transmission conditions in endemic areas.

Tchakoute VL et al. (1999) Parasitology "Chemoprophylaxis of Onchocerca infections: in a controlled, prospective study ivermectin prevents calves becoming infected with O. ochengi."

Bronsvoort M, Trees AJ, Renz A, Tchakoute VL, Tanya V

[Parasitology, 1999]

Onchocerciasis ('River Blindness'), caused by the filarial nematode Onchocerca volvulus is of major public health importance in West Africa. Ivermectin, a drug originally developed for veterinary use, is now being incorporated in control strategies but whilst it has potent efficacy against L1 larvae (microfilariae), ivermectin is not lethal to adult (L5) O. volvulus, nor to adults of the related cattle parasite O. ochengi. We have exploited this model to determine if ivermectin has prophylactic activity against naturally transmitted, O. ochengi infections in a controlled, prospective study in northern Cameroon. Calves were treated monthly with ivermectin at either 200 micrograms/kg or 500 micrograms/kg for 21 months. None of 15 treated calves developed adult worm infection, whereas 5/6 untreated controls became infected (P < 0.001) with a total of 54 O. ochengi nodules, and all 5 developed patent microfilaridermia. These results have significant implications for the use of ivermectin in humans, and suggest that strategic chemotherapy at times of maximal transmission will confer prophylactic as well as therapeutic benefits.

Achukwi MD et al. (2004) Vet Parasitol "Onchocerca ochengi acquisition in zebu Gudali cattle exposed to natural transmission: parasite population dynamics and IgG antibody subclass responses to Ov10/Ov11 recombinant antigens."

Renz A, Bradley J, Harnett W, Achukwi MD

[Vet Parasitol, 2004]

Ngaoundere Gudali zebu cattle naturally exposed to Simulium damnosum s.l. and Culicoides spp. bites were examined during 4 years for O. ochengi adult worm acquisition, Onchocerca ochengi and Onchocerca gutturosa skin microfilaria dynamics, and IgG1 and IgG2 antibody subclass responses. Eleven animals acquired a total of 465 O. ochengi nodules (average of 17 per female and 72 per male). The O. ochengi nodule load was highly variable in individual animals and exacerbated in mature male cattle. Three patterns of acquisition of O. ochengi (resistant to new infestation, early susceptibility and late susceptibility), not associated with Simulium biting intensity (P > 0.05), were distinguished. The minimum prepatent periods for O. ochengi nodules, O. ochengi microfilariae and O. gutturosa microfilariae were 10, 20 and 21 months, respectively. The O. ochengi microfilaria density significantly (P < 0.001) increased with age, was higher in young mature bulls than female animals (P < 0.001) and finally reached highest levels (P < 0.005) during the dry season. Antibody responses to Ov10/Ov11 recombinant O. volvulus antigens were predominantly of the IgG1 subclass. High levels of this subclass (not IgG2) observed in new born calves declined to almost zero levels at the age of 5-8 months but IgG1 levels significantly increased (P < 0.05) with age subsequently during patency. Put together the acquisition and accumulation of O. ochengi parasites in zebu cattle, apart from being season, sex (gender) and host age associated, may also suggest a density-dependent regulation of parasite establishment in a proportion of the exposed population.

Dec Bronsvoort BM et al. (2008) Parasit Vectors "UMF-078: A modified flubendazole with potent macrofilaricidal activity against Onchocerca ochengi in African cattle."

Ekale D, Dec Bronsvoort BM, Tanya VN, Trees AJ, Makepeace BL, Fleckenstein L, Renz A

[Parasit Vectors, 2008]

UNLABELLED: Human onchocerciasis or river blindness, caused by the filarial nematode Onchocerca volvulus, is currently controlled using the microfilaricidal drug, ivermectin. However, ivermectin does not kill adult O. volvulus, and in areas with less than 65% ivermectin coverage of the population, there is no effect on transmission. Therefore, there is still a need for a macrofilaricidal drug. Using the bovine filarial nematode O. ochengi (found naturally in African cattle), the macrofilaricidal efficacy of the modified flubendazole, UMF-078, was investigated. METHODS: Groups of 3 cows were treated with one of the following regimens: (a) a single dose of UMF-078 at 150 mg/kg intramuscularly (im), (b) 50 mg/kg im, (c) 150 mg/kg intraabomasally (ia), (d) 50 mg/kg ia, or (e) not treated (controls). RESULTS: After treatment at 150 mg/kg im, nodule diameter, worm motility and worm viability (as measured by metabolic reduction of tetrazolium to formazan) declined significantly compared with pre-treatment values and concurrent controls. There was abrogation of embryogenesis and death of all adult worms by 24 weeks post-treatment (pt). Animals treated at 50 mg/kg im showed a decline in nodule diameter together with abrogated reproduction, reduced motility, and lower metabolic activity in isolated worms, culminating in approximately 50% worm mortality by 52 weeks pt. Worms removed from animals treated ia were not killed, but exhibited a temporary embryotoxic effect which had waned by 12 weeks pt in the 50 mg/kg ia group and by 24 weeks pt in the 150 mg/kg ia group. These differences could be explained by the different absorption rates and elimination half-lives for each dose and route of administration. CONCLUSION: Although we did not observe any signs of mammalian toxicity in this trial with a single dose, other studies have raised concerns regarding neuro- and genotoxicity. Consequently, further evaluation of this compound has been suspended. Nonetheless, these results validate the molecular target of the benzimidazoles as a promising lead for rational design of macrofilaricidal drugs.