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Biomedical subjects

B O Duke

Publications and source records attributed to B O Duke.

At least 55 records · Page 3Linked to original sources

The use of a molluscicide in conjunction with chemotherapy to control Schistosoma haematobium at the Barombi Lake foci in Cameroon. III. Conclusions and costs.

Although Frescon successfully controlled snails on the margins of the Barombi lakes, and although the continuation of niridazole and Frescon control reduced transmission of S. haematobium very considerably, practical difficulties, which are discussed, rendered the twin goals of snail- and parasite-eradication impossible to achieve. The "break-point" in transmission of S. haematobium appears to lie so low as to be practically synonymous with total eradication. Control operations would thus have had to be maintained indefinitely in order to avoid a rapid return to the pre-control situation. The cost of the control element in this combined chemotherapeutic and molluscicidal research project, at 2 lacustrine foci of S. haematobium transmission in the United Republic of Cameroon, was 9 to 10 U.S. dollars per year per head of population protected. This sum is about three times the country's total estimated expenditure per head of population on all health and social services for the year 1974-1975. The high cost of such operations is only likely to be acceptable where schistosomiasis causes much ill-health and reduced economic productivity, and where tangible benefits may be expected from a reduction in the intensity of infections, short of eradication.

Bulinus↗

Fundus lesions in the rabbit eye following inoculation of onchocerca volvulus microfilariae into the posterior segment. II. Pathology.

The injection of living microfilariae of Onchocerca volvulus into the vitreous or immediately beneath the retina of rabbits gave rise to a variable degree of choroiditis. Uveal inflammation was most marked in eyes inoculated directly into the retina and subretinal tissue. The choroiditis was characterised by lymphocytic, plasma cell and eosinophil infiltration and was associated in many instances with degeneration of the overlying retina and pigment epithelium. In the eyes of animals killed more than 40 days after inoculation with microfilariae the leucocytic infiltration was usually mild or even absent, and the predominant finding was circumscribed atrophy and degeneration of the retina. It is concluded that the pathogenesis of the lesions in posterior segment onchocerciasis is basically inflammatory with, possibly, a direct toxic action of the microfilariae on the retina.

Animals↗

Fundus lesions in the rabbit eye following inoculation of onchocerca volvulus microfilariae into the posterior segment. I. The clinical picture.

Live microfilariae of the Cameroon forest and Sudan-savanna strains of Onchocerca volvulus were inoculated into the vitreous or into the subretinal layers of the eyes of rabbits. The lesions produced are described, and are compared with those seen in control animals, which had received inocula of microfilariae-free saline supernate introduced with a similar degree of operative trauma. Control rabbits showed only minor pigment disturbance in the retina and choroid, near the healed operation scars. Infected animals showed evidence of an inflammatory process in the eye, lasting for up to 4 weeks. Fundus lesions developed following inoculation of microfilariae into the vitreous, but they were more frequent and more severe following subretinal inoculation. The lesions produced were: pallor, vascular narrowing, and flattening of the optic disc; subretinal inflammatory exudate, giving rise to a disturbance of pigment in the retinal pigment epithelium; scattered, small choroidoretinal scars, and larger circumscribed areas of choroidoretinitis, sometimes accompanied by optic atrophy. In many eyes inoculated with microfilariae the wincing reflex was lost, indicating some visual impairment. Many of the lesions were similar to those seen in human patients with onchocerciasis, but they developed much more rapidly. Microfilariae inoculated intravenously, or into the periocular tissues, were not observed to penetrate into the eye-ball.

Animals↗

Microfilariae in the cerebrospinal fluid, and neurological complications, during treatment of onchocerciasis with diethylcarbamazine.

Microfilariae of Onchocerca volvulus were found in the cerebrospinal fluid (CSF) of 5/8 heavily infected onchocerciasis patients. During treatment with diethylcarbamazine citrate 10/11 patients showed increased numbers of 0. volvulus microfilariae in the CSF. Patients with concentrations of 8-31 mf/ml CSF developed severe vertigo, and some other neurological manifestations, during treatment. A hypothesis is put forward to account for this clinical piciture, and its importance in relation to the treatment of onchocerciasis is discussed.

Arachnoid↗

The populatin dynamics of Onchocerca volvulus microfilariae during treatment with suramin and diethylcarbamazine.

During treatment with suramin the numbers of O. volvulus microfilariae in the blood, urine, sputum, and anterior chambers of the eye fell before those in the skin. When diethylcarbamazine (DEC) was given after suramin, increased numbers of microfilariae appeared in the blood, urine, cerebrospinal fluid (CSF) and sputum, but the increase in the blood was less marked, and of shorter duration, than in similar patients receiving DEC without previous suramin. Microfilariae are thought to enter the urine, sputum and CSF directly from the blood by penetrating the capillary walls in the glomeruli, pulmonary alveoli, and choroid plexuses. Those in the aqueous humour do not appear to come directly from the bloodstream. The total numbers of microfilariae in the skin of some heavily infected onchocerciasis patients are estimated, as are the total numbers moving into the blood-stream under the influence of DEC and the proportion which escape into the urine, sputum and CSF. It is concluded that the majority of the microfilariae which appear in the blood during DEC therapy must be destroyed in the body, probably in the liver.

Anterior Chamber↗

Antigenic diversity among Onchocerca volvulus in Nigeria, and immunological differences between onchocerciasis in the savanna and forest of Cameroon.

Onchocerciasis is a remarkably chronic infection and, in West Africa, there are distinct clinical and pathological differences between the disease in the savanna and in the forest. Experiments were carried out to see whether antigenic diversity among Ochocerca volvulus worms might contribute to these features. Extracts of adult worms and or microfilariae were analysed by disc electrophoresis on polyacrylamide gels and showed a remarkable diversity of protein patterns but no consistent savanna/forest or Nigeria/Cameroon differences. Indirect haemagglutination using cross-absorbed sera was used to look for antigenic diversity or identity between different O. volvulus worms. Sera of patients were absorbed with antigens extracted from worms taken from those paitents and then titrated against sheep erythrocytes coated with the same antigens. It was shown that an adult Onchocerca volvulus could be either antigenically identical with, or distinct from, another worm taken from the same patient. In one Nigerian village identity was shown in two instances nad diversity in five. Microfilariae lack some antigens possessed by adult worms. This test has shown consistent savanna/forest differences in worm antigen patterns and antibody responses. In order to explain the pattern of these differences it was necessary to postulate that forest patients possessed antibodies to another worm which had antigens in common with savanna Onchocerca. The relevance of these findings to the pathology and prevention of onchocerciasis is discussed.

Antigens↗

The use of a molluscicide, in conjunction with chemotherapy, to control Schistosoma haematobium at the Barombi Lake foci in Cameroon. I. The attack on the snail hosts, using N-tritylmorpholine, and the effect on transmission from snail to man.

The background and strategy of a campaign to control the transmission of Schistosoma haematobium at the isolated crater-lake villages of Barombi Mbo and Barombi Kotto are outlined. A two-pronged attack was envisaged, using N-tritylmorpholine (Frescon) to control the snail host, and niridazole (Ambilhar) to control the parasite in man. The lake villages and their environs are described. Observations, relevant to control, are recorded on the biology of Bulinus rohlfsi and B. camerunensis. Snail populations were sampled by hand picking, and by the use of basket traps baited with dead leaves. Some experiments on the susceptibility of both snails to S. haematobium are described, together with observations on the strains of schistosome developing in monkeys exposed to cercariae from naturally-infected snails from the lakes. Frescon was applied through a tube to the bottom layers at the edge of the lakes, where the snails lived. Concentrations of 2 ppm down to 0.5 ppm N-tritylmorpholine proved necessary for adequate kills. Intervals of 6 weeks between treatments sufficed to control B. rohlfsi, but applications every 2 weeks were needed for B. camerunensis. The numbers of egg-masses, of snails, and of infective snails of both species were recorded before, during and after Frescon/Ambilhar control; and snail transmission rates and indices have been calculated. Control operations reduced transmission by R. rohlfsi to 2.4% of the pre-control level, or to below the detectable threshold. They were most effective at Mbo, where B. rohlfsi was the only intermediate host. At Kotto, despite excellent B. rohlfsi control, transmission of the residual infections in the human population by B. camerunensis persisted during control operations, until the intervals between Frescon applications were cut to 2 weeks.

Animals↗

The differential dispersal of nulliparous and parous Simulium damnosum.

Dissections of Simulium damnosum in the Sudansavanna zone of Cameroon indicated that nulliparous flies dispersed mainly inland away from their riverine breeding sites. Parous flies also dispersed inland to the same distances as nulliparous flies, but mainly they stayed close to, or moved along, the banks of the breeding rivers. This tendency was most marked in the older parous flied. As a result of this differenital dispersal, the numbers of S. damnosum carrying infective larvae of Onchocerca volvulus were highest on the banks of breeding rivers. This has an important bearing on the epidemiology of onchocerciasis. Tests at one place in Guinea savanna indicated a similar dispersal pattern there. In the forest zone nulliparous flies tended to stay near the rivers; and the proportions of parous and of infective flies were higher inland than on the river bank.

Animals↗

The Onchocerca volvulus transmission potentials and associated patterns of onchocerciasis at four Cameroon Sudan-savanna villages.

The intensity of O. volvulus infection, and the prevalence of certain eye lesions and of blindness, are compared in 4 hyperendemic Cameroon Sudan-savanna villages. The pattern of the disease is related to the annual transmission potentials to which the communities were exposed, and the results are compared with those obtained previously in forest villages. The prevalence and intensity of O. volvulus infections in S. damnosun were more closely related to the prevalence of positive skin snip than to the mean concentrations of microfilariae in the skin. Owing to the differential dispersal of nulliparous and parous flies in savanna, the annual transmission potentials were related more closely to the numbers of parous flies than to the total fly population. Factors governing the exposure of persons to infective flies are discussed. Seasonal transmission, which was usually light, did not lead to severe onchocerciasis; the more perennial the transmission the heavier was its degree, and the more prevalent were eye lesions and blindness. Annual transmission potentials of about 500, 1750, 1800+ and 2900 were associated with an increase in the mean intensity of infection and in the prevalence of eye lesions, while the onchocerciasis blindness rate in persons over 20 years old rose from nil to 3.3, 9.2 and 10 per cent respectively. Annual transmission potentials of 4400 and 19000 were recorded on the banks of S. damnosum breeding rivers in the area, but no villages were sited at such places and it is probable that no community could survive under such conditions. The bearing of these findings on the anticipated effects of S. damnosum control operations in savanna is discussed.

Animals↗

Reactions to subconjunctival inoculation of Onchocerca volvulus microfilariae in pre-immunized rabbits.

Rabbits, pre-immunized by intravenous inoculations of live, or of freeze-killed microfilariae of Onchocerca volvulus, were later challenged by subconjunctival inoculation of live microfilariae. Those pre-immunized with live microfilariae showed a marked chemotic conjunctivitis and reactions in the cornea (stromal keratitis and limbal abscesses), starting within one day of challenge. They were classed as sensitized. Those pre-immunized with dead microfilariae produced minimal reactions also starting on day 1, and were classed as tolerant. Histologically the reactions were distinctly greater in sensitized than in tolerant animals. The predominant cells in the inflammatory exudate were polymorphonuclear leucocytes and lymphocytes. The immunological basis for the differences between sensitized and tolerant rabbits is discussed, together with its possible bearing on human onchocerciasis. The effects of long-term subconjunctival and sclerocorneal inoculation of microfilariae were compared in one sensitized, one tolerant, one previously exposed, and one sensitized control rabbit. The sensitized test animal showed lesions resembling the sclerosing keratitis of human onchocerciasis. Immature microfilariae taken from intra-nodular fluid showed little ability to penetrate the cornea of the rabbit, and were minimally pathogenic.

Animals↗

Factors influencing the passage of Onchocerca volvulus microfilariae into the urine.

The effect of various substances on the output of Onchocerca volvulus microfilariae in the urine was investigated in volunteers infected with the Cameroon forest and Sudan-savanna strains of the parasite. Output of microfilariae in the urine tended to be higher during periods of normal activity than during sleep. During waking hours, the rate of output remained generally steady, but in some patients occasional showers of microfilariae appeared in the urine, possibly associated with the intake of food and drink. Drinking 1.2-2.5 litres water produced a shower of microfilariae in the urine of some subjects. This began within an hour of drinking and its onset preceeded that of the diuresis. Thiazide diuretics, acting on the convoluted tubules, produced no increase in microfilaruria. In savanna subjects intravenous injection of DT TAB vaccine caused pyrexia, and simultaneously large numbers of microfilariae appeared in the urine. There was no associated diuresis, and no increase in the concentration of microfilariae in the venous blood. In forest subjects DT TAB caused no increase in microfilaruria. In all subjects 25-50 mg diethylcarbamazine (DEC) caused large numbers of microfilariae to appear in the urine on day 0, within a few hours of the first dose; and there was an increased output of urine over the first 24 hours. Microfilaruria declined sharply on day 1 of treatment, but in subjects developing a high microfilaraemia, it rose again on day 2, and declined more slowly thereafter. Betamethazone, given in conjunction with DEC, appeared to slow the rate of destruction of microfilariae in the skin and lymph glands, and to prolong the duration of microfilaraemia and microfilaruria. The findings suggest that there is a reservoir of microfilariae in the glomerular capillaries, which fills slowly by accumulating microfilariae from the circulating blood. The microfilariae probably enter the urine by penetrating the glomerular capillary.

Adult↗