A.W. Woodruff

Anaemia in African trypanosomiasis and ‘big spleen disease’ in Uganda

Abstract Anaemia is common in African trypanosomiasis and in ‘big spleen disease’ in Uganda and its presence raises the question whether it could have an immunological basis. If an immunological mechanism is responsible, complement coating of the erythrocytes is likely to occur. Erythrocytes from patients with African trypanosomiasis and from others with ‘big spleen disease’ in Uganda were examined with an anti-complement serum. The presence of complement coating on the cells was demonstrated. Studies with chromium 51 in these patients also showed shortening of the erythrocyte life span with, in some, accumulation of radioactivity in the spleen resulting presumably from erythrophagocytosis within it. It is concluded that in active trypanosomiasis and in ‘big spleen disease’ in Uganda immune cytolysis contributes to anaemia and splenomegaly and that such a process long continued results in the development of the gross splenomegaly encountered in ‘big spleen disease’.

Mechanisms involved in the anaemia of schistosomiasis

1. 1. In normal and T.O. mice in this laboratory the 51CrT12 was found to be 13 days but in mice infected with S. mansoni this value was reduced to 5 days. 2. 2. This shortening of erythrocyte life span in the infected mice was associated with anaemia, no significant blood loss from the bowel but with some compensatory increase in bone marrow activity thus indicating that the anaemia was haemolytic, not dyshaemopoietic, in origin. 3. 3. Studies of splenic radioactivity indicated that the red cells of shortened life span were largely destroyed in the spleen. 4. 4. It was shown that infection with 1,000 irradiated and with 100 non-irradiated cercariae produced infections in the mice with similar numbers of adult schistosomes no ova accumulated in the tissues of the animals infected with irradiated cercariae. 5. 5. In animals infected with irradiated or non-irradiated cercariae anaemia developed but was slower to develop and less severe in the group infected with irradiated cercariae. 6. 6. The 51CrT12 in the anaemia with infections produced by irradiated cercariae was 8 days as contrasted with 5 days in their counterparts with infections from non-irradiated cercariae. The only detectable difference between the two groups was that those with the infections from non-irradiated cercariae also accumulated ova in thier tissues i.e. acquired a larger amount of helminthic antigen. Cirrhosis of the liver did not develop in the animals infected with ordinary cercariae. 7. 7. The conclusion is reached that anaemia in these animals is, at least in part, of immunological origin and an autoimmune process appears probable.

The direct antiglobulin test and immunoconglutinin titres in patients with malaria

Abstract The erythrocytes of 13 23 patients with clinical malaria were agglutinated at some time by anti-non-gamma globulin sera in contrast to 1 23 samples from control normal persons. Samples from patients and controls were handled in parallel from the moment of sampling onwards. The immunoconglutinin titre of the serum was raised in 6 10 patients with clinical malaria.

The mechanism of anaemia in kala-azar a study of 2 patients

Abstract Two patients with proved visceral leishmaniasis were studied with radio-iron 59Fe and radio-chromium 51Cr respectively, in an attempt to elucidate some of the mechanisms producing anaemia in this disease. The red cell life span was shown to be greatly reduced, with sequestration and probable haemolysis occurring in the spleen. The ferrokinetic studies suggested a mild degree of ineffective erythropoiesis. Blood volume determinations were normal.

Onchocerciasis in Guatemala. A clinical and parasitological study with comparisons between the disease there and in East Africa.

Abstract A clinical and parasitological study has been carried out in Guatemala by observers who had carried out a similar study, using similar methods, at Amani, Tanzania. Some quite large differences were encountered in the frequency of various clinical, including ophthalmological, features in the two series. These differences included a greater frequency of iritis and keratitis, particularly severe sclerosing keratitis, but not of fundal lesions, in Guatemala and a lower frequency of skin lesions especially those of the legs. Mal morado, erisipela de la costa and leonine facies were encountered exclusively in Guatemala and occurred among the more heavily infected subjects. Differences were also encountered in the density and distribution of microfilariae in the body of Guatemalan and African subjects. Microfilarial densities in the legs were low in Guatemala and those in the upper part of the body proportionally higher, but even the heaviest loads in Guatemala were rather lighter than those encountered in East Africa, and differences were not sufficient to account for the differing frequency of clinical features. Differences in density and distribution of microfilariae do not wholly explain the different incidence and severity of these clinical and ophthalmic findings. In particular, similar parasite densities are associated with more keratitis and iritis in Guatemala than East Africa. This could result from the two strains of parasite being fundamentally different or from differing responses to similar parasite loads by Guatemalans compared with East Africans. In the Guatemalan series iritis and keratitis were associated with significantly higher parasite loads than in those free from ocular lesions. In endemic regions of Guatemala more people in early age groups were found to be infected than in East Africa. Density of microfilarial load was found in Guatemala as in East Africa not to increase significantly after the age of 20, suggesting the development of immunity or a change in habits with increasing age leading to limitation of the number of infective bites sustained.

Clinical trials with entamide furoate and related compounds I. In a non-tropical environment

Abstract 1. 1) In a non-tropical environment where reinfection can be discounted, three derivatives of dichloroacet-4-hydroxy-N-methylanilide (Entamide), the benzoate, piperazine sulphate and the furoate have been tried in human infections with Entamoeba histolytica . 2. 2) Entamide benzoate, 40 mg./kg. body weight daily for 10 days resulted in disappearance of parasites from the stools in an average of 3.6 days, and of 15 patients passing cysts who were followed-up after treatment there were two relapses. 3. 3) Entamide piperazine sulphate, 30 mg./kg. body weight daily for 10 days resulted in disapperance of parasites from the stools in an average of 4 days, and of 14 chronically infected, treated and followed-up, one relapsed. Two patients having acute amoebie dysentery were treated of whom one relapsed. 4. 4) Entamide furoate, 20 mg./kg. body weight daily for 10 days resulted in disappearance of parasites from the stools in an average of 3.4 days, and of 30 in whose faeces cysts were present and who were followed-up after treatment one relapsed. Three patients with acute amoebic dysentery were treated of whom two followed-up did not relapse.

Symposium on the treatment of human amoebiasis II. The treatment of intestinal amoebiasis with emetine bismuth iodide, glaucarubin, dichloroacet-hydroxy-methylanilide, camoform and various antibiotics

1. (1) At the Hospital for Tropical Diseases, London, 417 patients suffering from intestinal amoebiasis have been treated and followed up under standard conditions. 2. (2) Emetine bismuth iodide was given in doses of 3 grains nightly for 10 nights to 220 patients. In 24 with E. histolytica trophozoites in the stool, this was preceded by 1 grain emetine by injection on 3 successive days. Of all these patients, 3 per cent. are known to have relapsed. 3. (3) The relapse rates :following treatment with chloramphenicol and aureomycin was so high that after short trials it was considered unjustifiable to continue the drugs. 4. (4) Of 14 patients followed up after treatment with oxytetracycline, two relapsed. 5. (5) Of 27 patients whose stools had contained E. histolytica cysts and who were followed up after treatment with fumagillin, one relapsed.Many toxic effects including dermatitis and albuminuria were encountered. 6. (6) Glaucarubin in doses of more than 4 mg. per kg. body weight was followed by a relapse rate of 12 per cent. among patients whose stools contained either E. histolytica cysts or trophozoites. 7. (7) A similar relapse rate followed the use of doses of 12 mg. or more dichloroacethydroxy-methylanilide in persons whose stools had contained E. histolytica cysts. 8. (8) It is concluded that emetine bismuth iodide is the most satisfactory drug at present available for the treatment of intestinal amoebiasis.

Toxocariasis in Africa and Malta. The frequency of infection in host animals and its incidence and distribution in humans as revealed by skin sensitivity tests.

Many of the clinical features of toxocariasis in man are commonly found in the tropics but they can also be caused by infection with other helminths; the prevalence of infection is therefore difficult to determine clinically. It had been shown previously that a toxocara skin sensitivity test was a useful epidemiological tool in the diagnosis of past or present toxocaral infection in humans and that the antigen did not give rise to significant numbers of cross positive or false positive reactions. Using this test, surveys were undertaken of the prevalence and distribution of toxocariasis in selected parts of Africa and the Mediterranean. Since infection can only occur in man if there is a considerable reservoir of infection in dogs and cats, surveys of the prevalence in dogs were performed simultaneously in the same regions as the surveys in humans. It was found that T. canis infection of dogs was prevalent in all the regions studied, and it was thought that the variations in the prevalence rates—from 36·5% and 28% infected in the humid areas of Ibadan, Nigeria and Dar-es-Salaam, Tanzania respectively, to 12% in the dry area of Masailand and only 6% in the cool of Nairobi, Kenya—were probably attributable to differences in the humidity and temperature in the different regions. In only a few cases could the age of the dog be established; in these cases the prevalence rate was higher in dogs of under one year compared to dogs of over that age. It was further found that in East Africa T. canis infection was less prevalent among owned than among stray dogs, and that this applied particularly to developed regions. Elsewhere such differences were not considerable, doubtless reflecting the similarity of the environmental conditions of owned and stray dogs in less developed regions. In human populations, analysis of the results of the toxocara skin test indicated that over the age of 10 years the prevalence rate of toxocariasis remains relatively stable. Comparisons between different regions were therefore made in respect of those aged 10 years and over. It was found that in Malta the prevalence of toxocaral infection (in man and dogs) was similar to that found previously in London, England. However, in Ibadan, Nigeria, higher rates of infection were encountered, and the hygienic conditions of the community together with the larger reservoir in host animals were considered to account for this. In Nairobi prevalence of toxocaral infection in dogs and man was low but in the Masai in the surrounding region although prevalence in dogs was low in comparison with Britain there was evidence of much transmission occurring from a smaller proportion of infected dogs than in Britain: in Dar-es-Salaam the proportions both of infected humans and dogs were greater than in Britain. The survey suggests that in all the regions studied, and therefore probably throughout the tropics, toxocariasis is a considerable health problem in man.

Onchocerciasis and the eye in western Uganda.

Abstract 1. 1) Earlier work has drawn attention to the possibility that intense infections plus another factor are required before vision is impaired in onchocerciasis. 2. 2) In the Bugoye region of Western Uganda intense onchocercal infections are found in the majority of the population and it is probable that all those who have reached early adult life are infected. The infection is principally transmitted by S. damnosum . 3. 3) Intensity of infection has become maximal in those of 30–39 years, and thereafter remains virtually unchanged for the next 20 years of life. 4. 4) Attention is drawn to the absence of pruritus in a significant proportion of patients with heavy onchocercal infections. 5. 5) Large inguinal or femoral lymphatic nodes, sometimes in pendulous sacks of skin, were encountered in eight of 67 patients. 6. 6) Ocular lesions including conjunctivitis, keratitis, iritis, and choroido-retinitis were encountered in some of the patients together with many non-onchocercal lesions causing impairment of vision. Anterior segment lesions were present in 29 patients, anterior and posterior segment lesions in 16, posterior segment lesions in eight and no ocular lesions in 14. 7. 7) Intensity of infection cannot be proved in this series to be associated with posterior segment lesions, but evidence was obtained suggesting that it may be so associated. 8. 8) No evidence in this study was found of vitamin A deficiency as a cause of choroidoretinitis in onchocerciasis. 9. 9) Evidence was also obtained that time, measured in decades rather than years, may be the principal factor which in addition to heavy onchocercal infection is required before impairment in visual acuity takes place.

Toxocara skin sensitivity tests and other observations in animals experimentally infected with Toxocara canis.

Abstract 10 white mice and 3 rhesus monkeys were used in an experiment to demonstrate the specificity of Toxocara skin sensitivity tests in the presence of infection with T. canis . 4 of the mice were used as controls, being either infected and tested with normal saline, or uninfected and tested with antigen; one of the monkeys remained uninfected but was tested with antigen. Injection of saline was used as a control throughout the experiment with the monkeys. The results show that negative skin reactions were obtained in all animals before infection with eggs of T. canis , but positive reactions occurred after variable periods in the animals infected, though not in the controls. The time of conversion of the skin test did not appear to depend on dosage. We conclude that the intradermal test with Toxocara antigen is specific for infection with T. canis and is therefore a valuable diagnostic test. The total white cell counts and eosinophil levels were recorded at intervals in the monkeys, and an increase in both was noted, reaching a peak the 3rd post-infection week and declining thereafter. No changes were observed in the total plasma proteins or in the albumin/globulin ratio. Inconclusive results were obtained with the filarial complement fixation test performed on the sera of the infected monkeys.