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Ivermectin is not lethal to the adult worms of Onchocerca volvulus or to those of O. ochengi, a cattle parasite closely related to O. volvulus. Although ivermectin penetrates the nodules in which the adults of these nematodes live, it is not known what levels of the drug enter the worms. Adult male O. ochengi were incubated in [3H]ivermectin in a saturated solution of unlabelled ivermectin (11.44 microM), to measure uptake by the oral and transcuticular routes, and in [3H]inulin, to ascertain if oral ingestion occurs in vitro. Uptake of [3H]ivermectin was high [1040 disintegrations/min (d.p.m.) at 3 h, representing a mean total of 86 pmoles ivermectin/worm] and occurred predominantly by the transcuticular route. Viability of worms was not reduced by this exposure, and uptake continued for up to 12 h. Only low levels of [3H]inulin (four d.p.m.) were detected in worms, indicating that the gut is probably not functional in vitro. Scanning and transmission electron microscopy revealed that the epicuticle of both sexes had an irregular surface which was pitted with a honeycomb structure in males, and rough and abundantly folded in females. These structures greatly increased the absorptive surface of the worms. In conclusion, ivermectin is able to enter adult O. ochengi males at concentrations sufficient to kill non-filarial nematodes.

For many years there was no suitable drug available for the control of onchocerciasis. The advent of Mectizan (ivermectin, MSD; an effective microfilaricide), its registration in October 1987 for the treatment of human onchocerciasis, and its suitability for large-scale application were major break-throughs in the control of human onchocerciasis via chemotherapy. Several studies, both fly-feeding experiments and community trials, have established that Mectizan treatment causes a significant reduction in the transmission of infection. Although long-term treatment in some isolated foci (such as occur in the New World and in some hypo- and meso-endemic areas elsewhere) appears to interrupt transmission, more prolonged treatment is required to prove if transmission can be stopped. Advantage could be taken of the significant impact of Mectizan on transmission by giving treatment while or just before transmission by blackflies is most intense.

The hundred men from a forest area of Ghana, without vector control or ivermectin distribution, were randomized to receive a single dose of ivermectin (150 micrograms/kg body weight) on day 1 followed by amocarzine (3 mg/kg twice daily after meals) on days 8, 9 and 10 (34 patients), the ivermectin alone (33 patients) or the amocarzine alone (33 patients). Detailed clinical and laboratory examinations were made before, during and after drug administration. On day 120, all palpable nodules were excised, fixed, sectioned, stained and examined by two blinded observers and the results compared with those for nodules from untreated controls. Mazzotti-type reactions, such as itching, rash, peripheral sensory phenomena and swellings, were more severe or frequent with amocarzine than ivermectin. Pretreatment with ivermectin markedly suppressed these reactions to amocarzine but did not affect other manifestations such as dizziness and gaze-evoked nystagmus. Ocular effects were minor in all groups. Ivermectin produced minor macrofilaricidal effects on the adult male worms, marked degeneration of intra-uterine embryos, and potent microfilaricidal effects and suppressed skin microfilariae. Amocarzine did not affect the male worms or the intra-uterine embryos, was a less potent microfilaricide and did not suppress skin microfilariae. The efficacy of ivermectin plus amocarzine was similar to that of ivermectin alone. The present results do not support the findings from the Americas and show that amocarzine has no role in the treatment of onchocerciasis in Africa.

The ocular disease associated with infection with Onchocerca volvulus is unique in that there is a wealth of epidemiological evidence to support the casual nature of the association but there is little known about the pathogenic mechanisms involved. We have identified a 44,000 M(r) component of ocular tissues that shows immunological cross-reactivity with an O. volvulus antigen. This immunological cross-reactivity between parasite and a component of host tissues may underlie the development of ocular disease in onchocerciasis. Preliminary experiments indicate that it is possible to initiate ocular disease in susceptible rats using the recombinant parasite antigen. This should allow the development of a laboratory model of ocular onchocerciasis and further our understanding of the mechanisms by which an infective organism can produce an auto-immune-like disease in the host.

Patients infected with Onchocerca volvulus in the Cayapa River focus in north-east Ecuador were given 500 mg chloroquine diphosphate (CQ) orally prior to nodulectomy. The concentrations of CQ were determined in parasite fragments and host tissue dissected from the nodules, in skin overlying the nodules, and in plasma at 3, 4, 7, and 24 hours after dosing. Onchocerca volvulus took up CQ rapidly, in some cases accumulating the drug to concentrations of over 600 pmol mg-1 worm tissue by three hours, and maintaining similar concentrations through 24 hours. These amounts were markedly higher than peak concentrations in plasma (3.16 pmol microliters-1) and in host tissues (78 pmol mgm-1) and skin (up to 93 pmol mg-1). In vitro uptake of CQ by females of O. volvulus was greater under alkaline conditions (pH 8.4) than at pH 6.8 and 7.4. Uptake reached equilibrium after one to two hours, with final concentrations being approximately 10 times lower than those reached in vivo. Inhibitory effects of chloroquine and its major metabolite desethylchloroquine on the motility of O. volvulus and other filariae have been observed previously in vitro; whether or not the drug had adverse effects on adult parasites in vivo was not determined in these experiments. However, the results illustrate the accessibility of O. volvulus to blood borne agents in vivo, and the potential importance of pharmacodynamic characteristics in the search for new macrofilaricidal agents.

Neonate Simulium females from an endemic area of human and bovine onchocerciasis in North-Cameroon were injected in one set of experiments with microfilariae (mff) of Onchocerca dukei and in another with mff of O. ochengi. Onchocerca dukei was found to develop to infective third-stage larvae in Simulium flies: 148 third-stage larvae (28.1% of injected mff) were recovered in S. hargreavesi, seven (10.4% of injected mff) in S. vorax, and 12 (1.3%) in S. damnosum s.l. Onchocerca ochengi mff developed in S. hargreavesi at a rate of 17.3% and in S. damnosum s.l. at 16.1%, yielding a total of 77 and 32 third-stage larvae respectively. Onchocerca dukei infective larvae had a mean length of 717.3 microns and a mean maximum diameter of 17.5 microns, and were slightly shorter and conspicuously thinner than those of O. ochengi (748.3 microns x 20.4 microns). All larval stages of O. dukei typically had an attenuated anterior end. The implications of these findings for the epidemiology of human onchocerciasis are discussed.

This paper presents some statistical problems of analysing changes in patterns of microfilarial loads in onchocerciasis patients after chemotherapeutic treatment. Analyses are made of a pooled set of data from ten separate studies of diethylcarbamazine (DEC) conducted at the Onchocerciasis Chemotherapeutic Research Centre, Tamale, between 1978 and 1983. Regression models of microfilarial load at different intervals post-treatment are fitted with initial microfilarial load, total dose of DEC, duration of treatment and age of the patient as the independent variables. Appropriate transformations of the variables are chosen by examination of plots of residuals for violations of the assumptions underlying the regression models. A dose response curve for DEC is produced.

Engorged females of three temperate simuliid species, Simulium ornatum, S. lineatum and S. equinum, were collected immediately after their bloodfeeds from a cow host. Midguts were dissected out at selected time intervals thereafter, from two minutes to 24 hours post engorgement (p.e.) and peritrophic membrane formation observed. There was an initial rapid secretion of peritrophic membrane (PM) material from the midgut epithelium. The peritrophic membrane produced is Type 1, being formed by delamination from the entire midgut epithelium. This secretory phase continued for approximately two hours p.e. in all three species and was followed by a period of organization within the membrane. At between 12 and 24 hours p.e., the PM appeared more organized and was associated with the formation of several distinct laminae in both S. ornatum and S. lineatum, although in S. equinum it consisted of only a single homogenous layer. Both the rate of secretion and the resulting morphological appearance of the PM appeared species-specific and there was great variation in its thickness in all three species at all time intervals examined. It is suggested that microfilariae penetrate the PM during the initial period of its secretion before it has condensed to form a distinct structure. Furthermore, the migration of microfilariae may be restricted to, or enhanced by, the presence of very thin areas within the membrane where erythrocytes lie almost adjacent to the midgut epithelium.

A case of idiopathic or Fournier's gangrene of the scrotum is described with unusual extension to the perineum. The clinical features of this disease are summarized. The literature is reviewed for extra genital extension of this gangrene of unknown aetiology. Coincidental association between infections with Onchocerca volvulus and scrotal gangrene was observed.

Microfilariae of Onchocerca volvulus were demonstrated by single shoulder-skin biopsy in 42.8% of inhabitants of seven Amerindian villages in an area of approximately 10,000 km2, near the Brasilian Roraima Territory. The highest prevalence was found among the Yanomama Indians of Chajurana (84.6%, with a mean of 61.3 microfilariae per mg of skin). The six other communities were affected, but with lower prevalence and microfilaria skin densities. The absence of lymphoedema and the few subcutaneous nodules and eye lesions found among the infected individuals suggest a relatively recent introduction of the disease to the region. Mansonella ozzardi infections were also detected in the area.

The sojourn times of the human population were monitored over one year at 12 sites in the vicinity of three villages in the Cameroon Sudan-savanna, where the Onchocerca volvulus transmission potentials had been measured one year previously. Boys stayed longer outside the villages, and were exposed 2.1 to 2.7 times more than girls to transmission of onchocerciasis, whereas the exposure of men was similar or only moderately higher than the exposure of women. In boys, the onset of infections and ocular lesions was earlier and the average microfilarial density at the buttock (2.2, 9.4 and 79.3 mff snip-1) was much higher than in girls (0.1, 5.8 and 42.2 mff snip-1 at the three villages respectively). These differences were maintained in the adult population, where the average microfilarial density was 52.3, 80.4 and 183.1 mff snip-1 in men and 15.6, 49.6 and 114.7 mff snip-1 in women. Ocular lesions due to onchocerciasis were found in 5, 13 and 55% of the male population in the three villages, as compared with 2, 3 and 8% of the female population. There was a close relationship between the degree of exposure to the transmission of disease and the resulting microfilarial load in the skin which was not different for the two sexes, and a similar trend was seen for the occurrence of ocular lesions due to onchocerciasis. The influence of an early and heavy infection on the evolution of disease manifestations is discussed.

A study of the prevalence of human onchocerciasis in eight villages around the Assob River in Jos Plateau, Nigeria, was undertaken between October 1983 and March 1985 using the skin-snip method. A total of 1673 individuals were examined. One hundred and eighty five (11.06%) had microfilariae of Onchocerca volvulus in their skin biopsies, and of these infected people, five (2.7%) were blind. The highest prevalence rate recorded was in Ngwan Madaki, where 51 (26.3%) of the 194 people examined were infected. The lowest percentage prevalence was recorded in Dogon Fili with four (1.95%) of the 205 people examined being positive. The proportion of infected people increased with age; and onchocercal lesions were significantly more common in older than in younger persons (P less than 0.05). There was no significant difference between infection rates in males and females (P greater than 0.05), although the overall percentage infection and the numbers of onchocercal lesions were higher in males than in females.

Previous studies of bovine Onchocerca spp. in cattle in Sierra Leone indicated that only O. gutturosa was transmitted in the forest zone at high intensity. To determine its vector(s) and the extent to which Onchocerca-like infections in Simulium damnosum were likely to be of bovine origin, three lines of investigation were pursued. Firstly, a study was made of the biting flies attacking an ox bait animal over a 14-month period at Njala University Campus, near Bo. Secondly, attempts were made to infect the dominant local forest cytospecies of S. damnosum s.l. with O. gutturosa by feeding them on an infected ox under a bed-net. Thirdly, S. damnosum s.l. were infected by intra-thoracic injection of O. gutturosa microfilariae (mff). In 113 collections made at dawn and dusk at weekly intervals from the ox bait, 624 simuliids and 7740 Culicoides spp. were collected. Almost all the simuliids were S. damnosum s.l. which, on the basis of iso-enzyme examination and knowledge of local breeding sites, were identified as S. soubrense 'B'. Although this cytospecies fed readily on the ox at ventral sites where O. gutturosa mff occurred and the bed-net experiments showed that 16.1% of engorged S. soubrense 'B' ingested an average of 3.3 O. gutturosa mff each, no development occurred. The refractoriness of S. damnosum s.l. to O. gutturosa was confirmed by the intra-thoracic injection experiments. The predominant Culicoides spp. attacking the ox bait were C. krameri, C. trifasciellus and C. fulvithorax, with smaller numbers of C. schultzei. In 5803 dissected Culicoides spp., natural infections of Onchocerca-like larvae, presumed to be O. gutturosa, were found in 0.3% of C. fulvithorax, 0.1% of C. trifasciellus and 0.06% of C. krameri. It was concluded that, in the forest zone of Sierra Leone, S. damnosum s.l. is not a vector of O. gutturosa and all Onchocerca-like larvae in S. damnosum are likely to be O. volvulus, while the natural vectors of O. gutturosa are the Culicoides species C. fulvithorax, C. trifasciellus and C. krameri.

(1983). Attempts to obtain a surrogate vector for bovine Onchocerca sp. Annals of Tropical Medicine & Parasitology: Vol. 77, No. 4, pp. 443-445.

The numbers of maturing oocytes in gravid Simulium damnosum s.l. were related to the sizes of the flies and when this was taken into account the numbers fell into two groups. It was concluded that the group with the highest oocyte counts were nulliparous and that the remainder were parous flies. No evidence was found to suggest that flies in their third or subsequent gonotrophic cycles matured fewer oocytes than those in their second cycles. However, the results did suggest reduced fecundity of those flies infected with Onchocerca spp. The frequency distributions of the Onchocerca spp. infections for each of three different stages can be fitted to negative binomial distributions with similar values (0·04–0·07) for the parameter k.

Six marking-recapture experiments were carried out with Simulium damnosum in the Cameroon Republic, five in the rain-forest and one in the Sudan-savanna zone. Adult flies were marked by applying a small spot of oil paint to the mesonotum while they were engorging with blood on the legs of volunteers infected with Onchocerca volvulus microfilariae. Catches of wild flies were carried out for 12-13 days after the first day of marking, and all marked flies recaptured were examined. Some of the flies recaptured on days 0, 1 and 2 were nulliparous and had probably been disturbed by the application of the paint before they had completed their blood-meal. The frequency distribution of recaptured marked parous flies returning for their "second" blood-meal rose to a peak early on day 4, but more flies returned earlier,three days after taking a blood-meal, than later on day 5. After day 5, the numbers of recaptured flies were too low to demonstrate any peaks corresponding to "third" and later blood-meals. The longest surviving fly was recaptured 10 days after marking. Twenty-six percent of the flies recaptured on days 3 and 4 contained developing O. volvulus larvae three-five days old, which had presumably been ingested as microfilariae during the blood-meal taken on day 0. Infective larvae first appeared in flies returning late on day 6, and the highest percentage of infective flies occurred on day 7. Infective larvae were found in recaptured flies until day 10, the last day on which marked flies were recovered. Of 929 flies marked on the Sudan-savanna experiment, three (0-32%) flies were recaptured. Two returned on day 4 and one on day 6.

Nineteen patients from an area of vector control in the savanna region of Northern Ghana, all with moderate to heavy infections with Onchocerca volvulus and some with ocular involvement, were treated with 50, 100, 150 or 200 micrograms kg-1 of ivermectin. Detailed monitoring of clinical and ocular reactions and of alterations in skin microfilarial counts and laboratory indices were carried out during the first 28 days. Microfilarial counts in skin snips and detailed ocular examinations were then repeated at intervals over a period of nine months. Ivermectin slowly eliminated microfilariae from the skin and eye without serious adverse clinical or ocular reactions in all treated groups. There was little difference in efficacy between doses of 100, 150 and 200 micrograms kg-1, and these were more effective than the 50 micrograms kg-1 dose. Very low levels of skin microfilariae were maintained for nine months. Microfilariae were not eliminated from the eye for at least three months. The drug was neither macrofilaricidal nor embryotoxic. However, it produced a dose-dependent stimulation of embryogenesis manifest at one month and succeeded by a suppression of embryogenesis at three months after therapy. In areas where transmission of onchocerciasis has been interrupted, ivermectin may need not be given more often than once a year. The efficacy of the drug on single dosage and the mild adverse reactions produced, if confirmed in subsequent controlled studies, would greatly simplify the treatment of onchocerciasis and would reintroduce new concepts of the role of chemotherapy in the control of onchocerciasis.

In view of the promise shown by temperate simuliids for laboratory colonization, the ability of Simulium ornatum and S. lineatum to support the development of Onchocerca volvulus was investigated. An injection technique is described for the introduction of O. volvulus microfilariae from a chimpanzee into female simuliids in the absence of a bloodmeal. RPMI 1640 medium, with penicillin, streptomycin and foetal calf serum, proved satisfactory as an inoculation medium. Third stage larvae were obtained in both S. ornatum and S. lineatum after seven days at 27 degrees C. The rate of development of the parasite in S. ornatum is recorded.

(1957). Aortic Onchocerciasis Due to Onchocerca Armillata in Cattle in Ghana, with Special Reference to the Morphology of the Parasite. Annals of Tropical Medicine & Parasitology: Vol. 51, No. 2, pp. 216-224.