Biomedical subjects
Publications and source records attributed to T F Marshall.
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Histochemical staining methods for acid phosphatase were used to study the differences among microfilariae of various West African strains of Onchocerca volvulus in both forest and Sudan-savanna onchocerciasis zones. The results have shown statistically significant differences in the staining patterns of microfilarial populations in the two zones. In the rain-forest areas, where onchocerciasis is transmitted by Simulium yahense, S. sanctipauli, S. soubrense and S. squamosum, there were no significant differences of microfilarial staining patterns in patients, by age and sex, between the three Simulium-Onchocerca complexes studied. There was a close relationship between the "strain differences", as revealed morphoenzymatically, and the clinical picture of the disease in both the forest and the Sudan-savanna zones. The present findings are in favour of the hypothesis that there are intrinsic differences in the strains of the parasite occurring in the two areas. The application of the histochemical means of parasite characterization appears to be a useful tool in differentiating strains of O. volvulus and could contribute towards a better understanding of the epidemiology of human onchocerciasis in different bioclimatic zones where the disease is endemic.
A study of the relationship between microfilaruria and onchocercal eye lesions has been carried out among 619 persons in 5 villages of North Benin. There is evidence of a significant relationship between microfilaruria and irreversible eye lesions in men aged 15-34 years. The association of microfilaruria with high numbers of microfilariae in the anterior segment of the eye occurs more in older men.
The antibody response to group C meningococcal polysaccharide vaccine was studied in a Nigerian village. Household clustering of poor responders to immunization was detected. Age had a marked effect on antibody response, maximal titres being obtained only in those over the age of 10 years. Children with malaria parasitaemia had a lower antibody response than those without parasitaemia and subjects with the genotype AA had a lower antibody response than those with the genotype AS. The antibody response to the vaccine was not influenced by mild degrees of malnutrition but children with clinical marasmus or kwashiorkor were excluded from the study.
A 2-year epizootiological study was carried out on Schistosoma bovis in cattle in an enzootic area of the Sudan. The prevalence of infection, as judged by the Pitchford fecal egg counting technique, was very high, approaching 90% in 1.5-year-old animals. There was, however, a lower prevalence in older cattle, and this trend was also seen with the fecal egg counts. This suggests that the cattle gradually acquire resistance to reinfection, particularly since there seems to be little age-related variation in the amount of water contact. Monthly incidence rates, estimated from fecal examinations of initially uninfected "tracer" calves showed a marked seasonal pattern, being much higher in the hot summer months, and snail infection rates showed a similar seasonal pattern. In addition, both the monthly incidence measurements and the snail infection rates showed that transmission was much heavier in 1976 than in 1977. Epizootics such as those recorded previously in this area presumably arise from exceptionally intense transmission years.
Epizootiological observations on Schistosoma bovis in cattle at Kosti, Sudan, showed a significant fall in age-specific prevalence and intensity with age, based on fecal egg count. To test the possibility that this is due to acquired resistance, Kosti cattle and a control group of cattle of similiar breed and age from a nonenzootic area were experimentally challenged with 70,000 S. bovis cercariae. Clinical observations showed very clearly that the Kosti cattle were able to withstand almost completely the effects of the challenge, whereas the controls developed lethal infections. Resistance was further demonstrated by clear differences between the two groups in terms of their body weights, hematological measurements, histopathological and pathophysiological responses, and worm and egg counts. The data suggested that the main basis of the resistance was a suppression of egg production by the worms from the challenge, rather than absolute prevention of their maturation. There was also evidence of a suppression of the fecundity of worms in the naturally infected Kosti cattle.
Previous work has shown that cattle can acquire a strong resistance to Schistosoma bovis infection following repeated natural exposure. Partial resistance to a laboratory challenge with S. bovis has also been demonstrated in calves after immunization with an irradiated schistosomular or cercarial vaccine. The aim of the present study was to see whether this type of vaccine could protect calves under the very different conditions of natural exposure to S. bovis in the field. Thirty 6- to 9-month-old calves were each immunized with 10,000 irradiated S. bovis schistosomula by intramuscular injection and 8 weeks later were released into an enzootic area along with 30 unvaccinated animals. The calves were followed up for 10 months, during which period protection was evidenced by a lower mortality rate, a slower rate of acquisition of infection, and lower fecal egg counts in the vaccinated calves. Necropsy of the survivors showed 60--70% reductions in worm and tissue egg counts of the vaccinated calves as compared to those not vaccinated.
In a total of 1977 males aged 5 years and over examined in 21 cluster samples on the coast of Tanzania, the overall rate for microfilariae of Wuchereria bancrofti was 32%. Hydrocoele and elephantiasis rates were 39% and 3%, respectively. The rates and severity of these 2 clinical manifestations increased in the older age groups. Both the microfilarial density and prevalence increased rapidly in the early age groups, followed by a levelling off and then a slight fall in old age. There was no association between microfilarial densities or rates and the overall prevalence of hydrocoele, but a negative association was demonstrated between microfilaraemia and hydrocoeles and elephantiasis. A comparison between the length of residence in an endemic area and the microfilarial and clinical sign rates showed evidence for the long incubation period for W. bancrofti and for the slow development of hydrocoeles and elephantiasis.
From a consecutive series of 7000 patients with head injuries admitted to the regional accident service, Radcliffe Infirmary, Oxford between 10 and 24 years earlier, every patient was taken who had been amnesic or unconscious for one week or longer. Of these 479 patients, all but ten were traced, and either the cause of death was established or the survivors examined. Ten years after injury 4% were totally disabled, and 14% severely disabled to a degree precluding normal occupational or social life. Of the remainder, 49% had recovered, and the rest were dead. Additionally, a selected series of 64 patients whose unconsciousness had been prolonged for a month or more were studied. Forty of these had survived between three and 25 years after injury and were re-examined. On the basis of age at injury, the worst state of neurological responsiveness, and the duration of posttraumatic amnesia, the outcome of head injury can be predicted reliably in most cases. Patients and relatives need more reassurance and simple psychotherapeutic support, especially in the first few months after injury. Extrapolation from our figures suggests that each year in England and Wales 210 patients survive totally disabled and another 1500 are severely disabled.
The intensity and prevalence of proteinuria and haematuria were studied with urinanalysis reagent strips in a Gambian community in which the intensity of infection with Schistosoma haematobium was high. The level of proteinuria present was shown to be related to the intensity of infection. Follow-up for 12 months showed that infected subjects with heavy proteinuria had a good prognosis. These findings suggest that the urinary protein in such subjects is likely to originate from lesions in the bladder and ureters and that advanced glomerular pathology is probably rare. The relationship of the levels of proteinuria and haematuria to the egg count suggests they may be parameters which could have value as indications for chemotherapy. Detailed study showed that the effect of treating all the subjects who had both 30 mg/100 ml or more of protein and at least a trace of haematuria would have been very similar to treating all those with an egg count of 200 ova/10 ml or more. Since urinalysis with reagent strips is very simple and rapid it could have a role in mass chemotherapy campaigns, particularly those aimed at the identification and treatment of heavily infected subjects.
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This paper describes further characteristics of the immunization of sheep against schistosomes using live, irradiation schistosomula. Sheep immunized with a non-virulent strain of Schistosoma mattheei were protected against a more virulent strain of the same species for over a year. As there was no evidence that the irradiated parasites were able to persist this long, it was concluded that the vaccine had induced a sterile resistance. Heterologous vaccination, using irradiated S. mattheei schistosomula to immunize against S. bovis or irradiated S. mansoni schistosomula to immunize against S. mattheei, failed to induce any protection.
A study of morbidity in Schistosoma mansoni infection was made in 593 Sudanese patients seen in a four-year period in Khartoum Civil Hospital. Clinical and laboratory findings were compared in three egg-count groups and in four clinical forms of the infection. Patients were divided into three levels of intensity of infection: light (up to 100 eggs/gram of stool), moderate (101--400 eggs/g) and heavy (more than 400 eggs/g). According to the presence or absence of visceral enlargement, infected subjects were divided into one of four clinical forms: intestinal, hepatic, hepatosplenic and splenic. Among the symptoms only the passage of blood in the stools was significantly related to intensity of infection, and fever was significantly related to the presence of hepatosplenic disease. Hepatomegaly and splenomegaly were significantly more frequent in the heavy infection group. Anaemia, eosinophilia, raised ESR and an increase in both serum alkaline phosphatase and serum globulins were significantly related to the intensity of infection. On the other hand, haematological and biochemical changes, as well as histopathological changes, were more marked and severe in patients with hepatosplenic disease. For comparison, the findings of 117 patients with S. haematobium infections and of 41 with dual S. mansoni/S. haematobium infections are included.
Three techniques were compared for counting microfilariae of Wuchereria bancrofti in blood specimens--a standard slide method, the counting chamber technique (CCT) and a membrane filtration technique (MFCT). The CCT was much more sensitive than the slide method, the difference in sensitivity between these two methods probably being due mainly to the loss of microfilariae during the dehaemoglobinizing process prior to staining in the standard slide method. There was good correlation between the techniques when 0.1 ml of finger-prick blood was examined by the CCT and 1 ml of venous blood by the MFCT. The number of additional positives revealed by the MFCT was ten of 275 (3.6%) subjects examined. The use of venepuncture for MFCT is impractical for field surveys in East Africa whereas a microfilarial count on 0.1 ml of finger-prick blood meets most of the criteria required of a field technique. The method is simple, quantitative and acceptable to the population. The results are reproducible, can be readily checked, the technique provides a useful and practical method for obtaining prevalence information following control schemes. The finding of a relatively low prevalence of microfilariae seen by both MFCT and CCT in children aged five to nine years from a highly endemic filariasis area agrees with the results of previous East African surveys carried out by blood smear and CCT.
Mast cell population density was determined in normal skin from two regions of the arm of several healthy men and compared with blood vessel density and histamine concentration in the same sites. Mast cell and blood vessel counts were made in 1--1.5 micrometer thick plastic sections, by light microscopy and tissue-histamine concentrations were determined by automated fluorimetric analysis. Statistically significant correlations were found between mast cell counts, blood vessel counts and histamine content in skin from the upper arm but no similar correlations were obtained in the forearm. Anatomical differences between the two sites may have been the cause of this discrepancy. Wide variations in mast cell counts and blood vessel density were found in different sections from the same biopsy samples which confirms the notion that dermal mast cells are unevenly distributed. Analysis of variance of the mast cell counts showed that the variance between sections from different blocks from the same biopsy samples was greater than the variance between adjacent biopsies. There was also a marked variation in the histamine content between biopsy samples from sites only 2 cm apart in the same subject.
In coastal Tanzania, an area where the microfilariae (mf) of Wuchereria bancrofti exhibit nocturnal periodicity, the administration of 2 mg diethylcarbamazine (DEC) per kg body weight in the daytime provoked mf to enter the peripheral blood. In persons on normal daily activities the daytime DEC provocative method proved to be as sensitive in detecting microfilaraemia as was the examination of night blood. Its use in routine surveys is therefore justified. Although mf densities by day and night were highly correlated (r = 0.83) they tended to be lower after provocative daytime DEC than in the corresponding night blood, except in very light infections. This method was also useful in assessing the parasitological response to mass chemotherapy with DEC, but, in comparison with the results of the night blood examinations, the sensitivity and magnitude of the counts in persons remaining positive progressively decreased as the period of DEC administration increased. A correction factor has to be calculated to take account of this, and/or additional night blood samples must be taken.The dose of 2 mg of DEC per kg body weight used was readily acceptable to the people in coastal East Africa, whose cooperation is difficult to obtain for night blood surveys. Apart from W. bancrofti, the only human filarial infection occasionally encountered in this area was Dipetalonema perstans. Because of the risk of a severe Mazzotti reaction the test is contraindicated in onchocerciasis endemic regions. Severe reactions may also occur in subjects with loaiasis.