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B O Duke

Publications and source records attributed to B O Duke.

At least 37 records · Page 2Linked to original sources

On the reproductive activity of the female Onchocerca volvulus.

Onchocerca volvulus worms, extracted from nodules by collagenase digestion, stained with haematoxylin and cleared in glycerol, were unravelled for longitudinal examination and later embedded in brain blocks for study of serial transverse sections. A classification system for female worms is proposed, based on the reproductive status of 446 worms from Guatemala, 94 from Liberia and 125 from Mali. They were categorized into fecund, inseminated specimens; uninseminated, but potentially fertile specimens, shedding ova destined to degenerate; worms changing from the uninseminated to the inseminated state and vice versa, which were few in number; old worms, with degenerate ovaries, whose genital tracts were either empty or had disappeared; and moribund or dead worms, characterized by loss of turgor, collapse and degeneration, calcification, or invasion by polymorphic, basophilic cells. Potentially fertile worms shed oocytes continuously and, when they were inseminated, embryonic development ensured. No evidence was found of a periodic cycle of reproduction. Inseminated worms were found in nodules without a male worm, and uninseminated worms in nodules harbouring male worms. Measurements are recorded of portions of the female reproductive tract and of the length of uterus occupied by the various embryonic stages in fully fecund worms. A significant difference in the length of the body behind the first and second ovaries was observed as between worms from West African savanna (Mali) and forest (Liberia). Limited observations were also made on meiosis in the oocyte, penetration of the oocyte by sperm, formation of the ovum, syngamy and zygote formation.

Animals↗

Human onchocerciasis--an overview of the disease.

The general characteristics of Onchocerca volvulus infection and its transmission are outlined in this overview of human onchocerciasis. The pathogenic role of the microfilariae, producing lesions of the skin, lymphatic system, eye and deep organs, are described, along with the main clinical manifestations of the disease. The global prevalence and distribution of onchocerciasis are given. Best estimates in 1985 gave 86 million persons at risk, 17.8 million infected, 336,400 blind and a like number suffering from severe visual impairment. The vast majority was in Africa. The impact of onchocerciasis on communities in the Sudano-Guinean savanna zone of Africa is outlined, emphasizing the very high blindness rates and the increased mortality among the blind. Communities so affected cannot remain economically viable. They are forced to desert their villages and the fertile land near rivers. The background to the establishment of the Onchocerciasis Control Programme in West Africa (OCP) is given and the successful 10-year results of this campaign, which is based on prolonged, regular Simulium larviciding, are outlined. In the context of the future of the OCP and of the control of onchocerciasis elsewhere in the world, the need for improved chemotherapy is discussed. The prospects for large-scale suppressive therapy have greatly improved following the registration of ivermectin in 1988 for use in human onchocerciasis. The potential and possible uses of this drug, as a single-dose, non-toxic microfilaricide, which excites very little Mazzotti reaction and has a prolonged microfilarial suppressant action, are discussed. It is considered that an effective non-toxic macrofilaricide is still a prime need for onchocerciasis control.

Africa↗

Dynamics of microfilariae of Onchocerca volvulus over the first 72 hours after treatment with ivermectin.

Changes in microfilaria (mf) densities in skin, blood and urine were followed over 72 hours in 8 Guatemalan patients who received invermectin (150 mcg/kg po in a single dose). After an initial increase at 6 hours, the significance of which is not clear, mf densities in skin snips decreased rapidly to reach 13% of their pre-treatment level by 48 hours and then fell much more slowly over the next 24-hour period. The fall in mf concentrations is thought to be mainly a result of movement away from the subepidermal layer. In contrast to what happens after DEC, it was not accompanied by any marked wave of microfilaraemia or microfilaruria, nor by the appearance of a papular rash, although brawny oedema of the skin sometimes developed. Reactions that occurred after ivermectin could not be correlated with the initial density of microfiladermia. It is hypothesized that the movement of mfs may be 1) into the deeper layers of the dermal collagen, 2) the subcutaneous fat, or 3) the lymphatic system.

Adult↗

Construction of Onchocerca volvulus cDNA libraries and partial characterization of the cDNA for a major antigen.

Adult Onchocerca volvulus were isolated from nodules removed from onchocerciasis patients at four locations--two in the West African Sudan-savanna region (near Bamako, Mali, and Touboro, Cameroon), one in a West African forest region (Kumba, Cameroon) and one near Guatemala City, Guatemala. Four different cDNA expression libraries were constructed in bacteriophage lambda gt11 using poly(A)+ RNA from the adult female worms. Individual cDNA clones of single copy genes were used to compare the genomes of parasites from the different locales and to show that the haploid genome of O. volvulus is 1.5 x 10(8) base pairs. About 1 in 700 recombinant clones in each of the four amplified cDNA libraries produces a fusion protein recognized by pooled human anti-O. volvulus antisera. Partial sequence determination of a 2.0 kb cDNA clone for an O. volvulus protein that induces an immunodominant response in rabbits revealed that this antigen has sequence similarities with Caenorhabditis elegans myosin and with schistosome paramyosin (which confers partial protection against schistosome infection). The four cDNA libraries have been deposited with American Type Culture Collection (ATCC), 12301 Parklawn Drive, Rockville, MD 20852, U.S.A., for general distribution under ATCC Number 37509.

Animals↗

Diagnosis and extirpation of nodules in human onchocerciasis.

The clinical search for onchocercal nodules, and their preferred sites on the body in different geographic areas are described and illustrated. The differential diagnosis of onchocercomata is discussed and figures on the frequency of false diagnoses are reported. The prevalence of adult Onchocerca volvulus in relation to the endemicity of infection, the age and sex of the patients, the localisation of nodules on the body, and the measures used to control onchocerciasis are discussed. Recommendations are made on the selection of patients for different medical studies. The technique of nodulectomy and the equipment needed are described.

Animals↗

Observations on Onchocerca volvulus in experimentally infected chimpanzees.

The paper describes observations made on 32 chimpanzees experimentally infected with Onchocerca volvulus. The mean pre-patent intervals for the Cameroon forest and the Guatemalan strains of O. volvulus were 13-16 months and 12-15 months respectively. That for the Cameroon Sudan-savanna strain was much longer, i.e. 22-23 months. The numbers of microfilariae found in the skins of animals infected with the Cameroon Sudan-savanna strain were also much lower than in animals infected with the other two strains. Long-term observations on infected animals showed that microfilarial infections had virtually died out 6.5-9 years after the last inoculation with infective larvae. Those animals which were inoculated with infective larvae in the head or above the waist tended to show a higher proportion of microfilariae in the upper parts of the body, than did those inoculated with infective larvae below the waist. In animals which showed adult worm-bundles on only one side of the body, the concentration of microfilariae was usually greater on that side of the body. Worm-bundles in the chimpanzee varied in size from 8 x 5 x 2 mm to 4 x 3 x 2 cm. Out of 47 worm-bundles found, only two were subcutaneous. The remainder lay deep in the tissues, most commonly adjacent to the posterior surface of the capsule of the hip joint. No onchocerciasis eye lesions were seen in any of the infected animals.

Animals↗

The effects of some drugs--pentamidine, stibocaptate, Hoechst 33258, F 151, compound 'E' and Nifurtimox--on Onchocerca volvulus in chimpanzees.

Several drugs were investigated for action against Onchocerca volvulus in chimpanzees. Pentamidine at 4 mg/kg daily for 16 days had no filaricidal action; nor did stibocaptate at 10 mg/kg monthly for 8 months. Hoechst 33258, a substituted bis-benzamidazole, showed micro- and macrofilaricidal activity; F151 (an arsenical compound) showed a purely macrofilaricidal action; and Compound E (a reaction product of Hoechst 33258 and F151) was micro- and macrofilaricidal. The toxicity of the three last-mentioned compounds was high, and further trials were not made. Nifurtimox, at doses of up to 40 mg/kg for 10 days, was shown not be microfilaricidal, but there was a suggestion that this drug may have some macrofilaricidal action.

Animals↗

Onchocercal dermatitis: ultrastructural studies of microfilariae and host tissues, before and after treatment with diethylcarbamazine (Hetrazan).

Specimens of skin from four Cameroon patients with severe onchocercal dermatitis, before and after treatment with diethylcarbamazine (DEC), were studied by light and electron microscopy. Microfilariae of Onchocerca volvulus have ultrastructural features resembling those of microfilariae of other genera. Between the surface layer of the cuticle and the trilaminate membrane, there is an electrolucent zone which is much wider in degenerating microfilariae than in intact microfilariae. Widening of the zone may result from DEC-induced release of component(s) of the cuticle, possibly collagen or mucopolysaccharide. Between the cuticle and dermal collagen there are granular deposits which might be immune complexes involving the collagenous component of cuticle. Others have shown that DEC does not kill microfilariae in vitro. Treatment with DEC presumably "unmasks" microfilariae in the skin so that they are recognized as foreign bodies and are destroyed by the host's defenses. Histiocytes and eosinophils are seen in close proximity to degenerating microfilariae. Enzymes from histiocytes and eosinophils might readily penetrate the cuticle altered by DEC treatment, and digest various components within the microfilariae. Alternatively, the widening of the electrolucent zone might result directly from the action of leucocytic or histiocytic enzymes, after the microfilaria has been killed by other mechanisms.

Adult↗

The use of a molluscicide in conjunction with chemotherapy to control Schistosoma haematobium at the Barombi Lake foci in Cameroon. II. Urinary examination methods, the use of niridazole to attack the parasite in man, and the effect on transmission from man to snail.

The use of niridazole, in conjunction with snail control, in an attempt to control the transmission of Schistosoma haematobium at 2 Cameroon crater-lake villages is described. Quantitative examinations of urines for S. haematobium eggs were made on the whole population before control began, at intervals during the maintenance of control, and again after control ceased. The methods and difficulties are described, and their accuracy is discussed. After each examination all accessible egg-passers were treated or re-treated with niridazole. The drug was well tolerated and effective. Most treated patients ceased to pass live eggs, and most of those who later became positive again were thought to represent reinfections rather than relapses. During the maintenance of snail control, niridazole treatment of the 'whole' community reduced the total load of S. haematobium eggs passed to less than 1 per cent of the pre-control figure; and repeated subsequent treatments maintained a level of the same order. Despite this, there remained at different times 0.6-50.9 per cent of persons passing small quantities of live eggs, and these were an important source of continuing transmission. The possibility that more than one strain of S. haematobium was involved is discussed. An index of transmission from man to snail is proposed and discussed in relation to determining the level of the "break-point" in transmission. Although combined niridazole/molluscicide control reduced transmission from man to snail by about 3 log cycles, the "break-point", which is thought to lie 4 or more log-cycles lower, was not reached. When control was stopped, transmission built up again, with the prevalence rate in man rising more rapidly than the intensity of infections.

Adolescent↗