Showing papers in "Transactions of The Royal Society of Tropical Medicine and Hygiene in 1973"

The epidemiology of cutaneous leishmaniasis in Ethiopia

Abstract: Parasites indistinguishable from those causing cutaneous leishmaniasis of man in Ethiopia were found in 3 widely separated localities in rock hyrax and phlebotomid sandflies. A close association between hyrax and the sandflies was demonstrated both in cliff and tree habitats. Procavia habessinica and Heterohyrax brucei were both shown to be reservoirs of the disease, and are thought to be the only significant ones. Phlebotomus longipes and P. pedifer are the vectors. Man intrudes on the hyrax/sandfly cycle, but in no way sustains it, and is an incidental host. This distinctive epidemiological system is thought to occur throughout the range of cutaneous leishmaniasis in Ethiopia.

Immunosuppression in Gambian trypanosomiasis.

Abstract: Cellular and humoral immune responses were studied in 38 patients with Gambian trypanosomiasis and compared with those of 43 matched controls. Expression of cell mediated immunity, induction of cell mediated immunity and expression of humoral immunity were all impaired in the patients with trypanosomiasis. It is suggested that immunosuppression induced by T. gambiense may contribute to the increased susceptibility to secondary infection observed in patients with African trypanosomiasis.

Enzyme variation in Plasmodium falciparum in the Gambia

Abstract: A study has been made of electrophoretic forms of enzymes of P. falcaparum in samples of blood from Gambian women and children. Variation was found in each of the 3 enzymes examined. 2 forms of parasite GPI, labelled GPI-1 and GPI-2, 2 forms of parasite LDH, labelled LDH-1 and LDH-2 and 3 forms of parasite 6PGD, labelled 6PGD-1, 6PGD-2 and 6PGD-3 were identified. Different combinations of enzyme forms occurred among different samples demonstrating genetic diversity of the parasite within and between blood samples. The distribution of enzyme forms among the samples suggested that the parasites belong to a single mendelian population. From statistical considerations of the distribution of enzyme forms among the samples it was estimated that the samples contained an average of about 2 parasite clones each. It was also possible to estimate the frequencies of variant forms of GPI among parasite clones as 0·62 and 0·38 for GPI-1 and GPI-2 respectively and LDH as 0·76 and 0·24 for LDH-1 and LDH-2 respectively. 6PGD-1 occurred in about 95% of blood samples showing activity of this enzyme, the remaining variants of 6PGD occurred in only 2 samples each. In many instances it was possible to identify the enzyme forms characterizing clones of parasite in individual blood samples, but rarely to estimate the actual number of clones present in a given sample. In a few samples, however, in which a single form of each enzyme occurred it could be estimated that probably only 1 parasite clone was present.

Egg output stability and the epidemiology of Schistosoma haematobium. Part II. An analysis of the epidemiology of endemic S. haematobium

Abstract: On the basis of observations of school children described in Part I, a model for the infective process of S. haematobium in man in the Misungwi area of Tanzania is put forward. On the basis of steady challenge by cercariae, effective concomitant immunity, exponential death of worm pairs, the observed variance of egg output at age 10, and constant ranking by infection level in early life, the behaviour of egg output patterns with age in the community is predicted. Expected curves of output are compared with those observed in cross-sectional survey of over 4,000 people at Misungwi. Agreement is close. This provides additional evidence for the occurrence of concomitant immunity to S. haematobium in man and suggests that immunity cannot be disregarded in epidemiological models of the infection. It is suggested that there are 3 phases in an age-cohort's experience of endemic infection: acquisition and increase of infection, a phase of decreasing worm load combined with concomitant immunity, and a steady state phase, with loss of immunity and reinfection balancing, in later life. The need for better data on the nature of human immunity to schistosomiasis becomes apparent.

Immunosuppression in Trypanosoma brucei infections in rats and mice

Abstract: In rats in which N. brasiliensis infection was superimposed on a previously existing T. brucei infection of 3 weeks' duration, the normal process of immune expulsion of adult worms did not occur, the production of circulating protective antibody (IgG) and of reaginic antibody (IgE) was grossly impaired and there was no increase in the numbers of mast cells in the intestinal villi. In contrast to this failure of humoral and immediate-type responses, cell-mediated immunity, as measured by oxazolone sensitization of mice with a T. brucei infection, still occurred to a significant extent although not so markedly as in uninfected mice. These results, which provide further evidence that infection with T. brucei may induce a significant degree of immunosuppression of the host, are discussed with particular regard to the aetiology of the phenomenon.

Leishmaniasis in Brazil: IX. Considerations on the Leishmania Braziliensis Complex:—Importance of Sandflies of the Genus Psychodopygus (Mangabeira) in the Transmission of L. Braziliensis Braziliensis in North Brazil

Abstract: At least 3 different parasites may produce cutaneous leishmaniasis in man in Brazil. Leishmania mexicana amazonensis is widely distributed and very common in wild animals, but rarely infects man because the vector is not anthropophilic. L. braziliensis guyanensis and L. braziliensis braziliensis have highly anthropophilic vectors and are thus the major causes of the disease in man. Infections with Leishmania b. braziliensis are described in 17 persons from an endemic area in the Serra dos Carajas, Para, north Brazil. A nearby Indian tribe (Xikrin) was examined and leishmanin skin-tests carried out on 116 individuals. No evidence of past or present infection was found, but strong positive reactions were noted in 83·9% adult males, 38·8% adult females, 14·3% male children and 4·8% female children. A total of 2,701 man-biting and rodent-biting sandflies were dissected and the guts examined for flagellates. Promastigotes were found in 3 out of 1,656 Psychodopygus wellcomei, 2 out of 175 Ps. paraensis and 1 out of 127 Ps. amazonensis. Hamsters inoculated with promastigotes from one Ps. wellcomei developed a typical L. b. braziliensis infection. The importance of sandflies of the genus Psychodopygus is stressed: Ps. wellcomei is of particular importance due to its tendency to bite man during the day and the fact that it is attracted to both man and rodents in large numbers. Nearly all the sandflies were caught at ground level. The absence of a large, arboreal population of man-biters suggests that the reservoir-hosts of L. b. braziliensis are likely to be terrestrial or frequently coming to the ground.

Urinary schistosomiasis in Egypt: Clinical, radiological, bacteriological and parasitological correlations

Abstract: 200 Egyptian boys and men with urinary schistosomiasis were studied by clinical evaluation, radiography, quantitative egg excretion, bacterial cultures, and tests of renal function. Results were analysed by age, by symptoms (clinical grade), by presence of polypoid vs calcified schistosomal lesions (radiological stage), by presence or absence of obstructive uropathy, and by response to antischistosomal treatment. Age—Increasing age correlated slightly with decreasing egg excretion. Obstructive uropathy, bladder calcification, ureterolithiasis, and bladder retention increased linearly with age; polypoid lesions decreased linearly with age. Clinical grade—Age increased with increasing symptoms. Symptomatic patients excreted more eggs than those without symptoms. Non-functioning kidney was associated only with moderate or severe symptoms; other variables did not correlate with the grades. Radiological stage—Age increased from stage 1 (polypoid lesions only) to stage 2 (polypoid and calcified lesions) to stage 3 (calcified lesions only), as egg excretion decreased. Other variables were not different among the stages. Obstructive uropathy—Patients with obstruction were older than those without, and had higher frequencies of ureteral stenosis, ureterolithiasis, and bladder retention. Maximal urine concentration and phenolsulphonphthalein excretion were decreased in patients with obstruction. Treatment—Patients with improved urograms (including obstructive uropathy) following treatment were younger, excreted more eggs, and more frequently were in radiological stages 1 and 2 than patients without improvement. Improvement did not correlate with specific antischistosomal drugs or with the final percent reduction of egg excretion. These results suggest that the course of urinary schistosomiasis may be from polypoid to calcified lesions (radiological stage 1 to 3), associated with increasing age and decreasing egg excretion. However, clinical grade, bacterial urinary-tract infection, obstructive uropathy, and abnormalities of renal function are not stage-dependent. Although older age is associated with greater severity of symptoms and increasingly frequent radiographic abnormalities, appreciable morbidity occurs at all ages and in all stages of the disease in Egyptians in hospital. Prediction of reversibility of schistosomal uropathy can be made on the basis of age, egg excretion, and radiological stage.

Leishmaniasis in Brazil: VIII. Observations on the phlebotomine fauna of an area highly endemic for cutaneous leishmaniasis, in the Serra dos Carajas, Pará State

Abstract: A study has been made of the phlebotomine fauna in an area highly endemic for Leishmania braziliensis braziliensis in forest of the Serra dos Carajas, Para State, Brazil, using human and rodent bait. A total of 23 different species were encountered, including 2 new sandflies, to be described at a later date. Over 92% of the total catch off man was made up by species of the genus Psychodopygus . Of these, Ps. wellcomei formed 65% of the total caught off man and 24·5% of the total off rodents. This species is of particular interest in view of its tendency to bite man throughout daylight hours. Once more we have confirmed that although Lutzomyia flaviscutellata may be the predominent species feeding on rodents, it is rarely taken biting man. Very few sandflies were captured above ground-level; and attempts to find the daytime resting places for the major man-biting species were unsuccessful. The relationship of rainfall to sandfly density is discussed. It is concluded that the population density of certain forest species may depend not so much on the quantity of rainfall, but more on the amount of water which persists in the topsoil in a given region.

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’.

Studies with the schistosomicide oxamniquine (UK-4271) I. Activity in rodents and in vitro

Abstract: A single oral or intramuscular dose of oxamniquine (6-hydroxymethyl-2-isopropylaminomethyl-7-nitro-1,2,3,4-tetrahydroquinoline) had potent schistosomicidal action against Schistosoma mansoni in mice and hamsters. No convincing activity was demonstrated against Chinese S. japonicum in either host, or against Nigerian S. haematobium in hamsters, although the schistosomicide hycanthone also was inactive orally against the latter. Male S. mansoni were markedly more susceptible than females in vivo but not in vitro. Against a Puerto Rican strain in mice the oral ED 50 and ED 99 values were 20 and 44 mg./kg. respectively given as a single dose, and 28·5 and 57·5 mg./kg. respectively given as 5 consecutive daily doses of 5·7 and 11·5 mg./kg.; by the intramuscular route ED 50 and ED 99 values were 18 and 42 mg./kg. respectively as single doses, and 19·5 and 37 mg./kg. respectively given as 5 consecutive daily injections of 3·9 and 7·4 mg./kg. There were strain differences in reaction to the drug. When administered orally against an East African strain in mice, oxamniquine was 2–3 times more potent than hycanthone, 5–11 times more potent than niridazole and 8–11 times more potent than lucanthone. Oral potency against Puerto Rican S. mansoni in hamsters was similar to that in mice, but intramuscular activity was considerably greater, the single dose ED 50 and ED 99 being only 6·7 and 12 mg./kg. respectively. The acute LD 50 in mice was 1,300 mg./kg. (oral) or more than 2,000 mg./kg. (intramuscular), and by multiple dose regimens toxic symptoms were produced only by doses greatly in excess of the curative levels. Observations in other species and safety tests in man confirmed the suitability of the compound for clinical trial.

Studies on the Anopheles punctulatus complex I. Identification by proboscis morphological criteria and by cross-mating experiments

Abstract: The progeny of 150 females of the A. punctulatus complex, collected in Northern Australia, the Territory of Papua and New Guinea and the British Solomon Islands Protectorate were studied. Cross-matings showed that these Anopheles belonged to 4 species: A. punctulatus, A. koliensis and 2 species which were previously recognized as A. farauti and now provisionally designated A. farauti No. 1 and A. farauti No. 2.

The trypanocidal action of human serum and of baboon plasma

Abstract: 1. 1. Investigations have been made on the activity of normal human serum, and of baboon plasma in killing non-pathogenic trypanosomes such as Trypanosoma equiperdum. Baboon plasma is 5 times more active than human serum but otherwise its activity is qualitatively the same. 2. 2. The activity varies according to whether it is measured in vitro or in vivo (i.e. in mice). It is postulated that there are 2 closely related substances, A which acts in vitro and B which acts in vivo. Usually both substances are present but in suitable circumstances they can be obtained separately. Most human and baboon sera contain much B, but some contain very little A. Usually there is 20–40 times as much B as A. 3. 3. In vitro, there is a lag period of about 34 hour and then trypanocidal action is completed in less than 6 hours. In vivo the action is a little slower. 4. 4. Substance A is suppressed if the human serum is injected intravenously into rats and mice but B is made more active. The substances could not be removed from serum by absorption with large numbers of trypanosomes. 5. 5. Human serum and baboon plasma were fractionated by ion-exchange chromatography and by gel filtration using Sephadex G-150 and Sepharose 6B. The active fractions were further examined by Laurell immunoelectrophoresis. These techniques indicated that the active substances are α2 macroglobulins with molecular weight approximately 300,000. B has a slightly greater molecular weight and is slightly more acidic than A. It is postulated that both substances possess the same protein nucleus, but that they differ slightly in the configuration and/or composition. Some sera, which were initially inactive in vitro, yielded highly active fractions after gel filtration; this activation might be due to conversion of B into A or to removal of inhibitors which were masking A. 6. 6. When trypanosomes are exposed to serum there is a latent period of half an hour, after which the trypanosomes become distorted until they are almost globular. As shown by the electron microscope, there is progressive disintegration of the cytoplasm and large clear spaces appear beneath the pellicle. The other structures of the trypanosome persist unchanged for a long period, but ultimately the trypanosome disintegrates. 7. 7. As shown above the trypanocidal substances are α2 macroglobulins and they are probably synthesized in the liver (not in the spleen and lymph glands). Accordingly their activity is quite different from the standard immunological processes. Their action might be due to either a coincidental stimulation of the serum protein by the surface of the trypanosome, or it might be a biological mechanism to protect men and baboons from many species of African trypanosomes, or that it might be part of a properdin system against infections in general. 8. 8. The trypanocidal action of human serum has been used by Rickman and Robson (1970) in the Blood Incubation Infectivity Test to differentiate T. rhodesiense from T. brucei. Improved methods for conducting and interpreting this test will be described in a second communication.

The nature of the establishment barrier for Trypanosoma brucei in the gut of Glossina pallidipes.

Abstract: The low survival rate of Trypanosoma brucei in tsetse flies is interpreted as in part at least the result of an establishment barrier. This barrier appears to be less active in young flies than in older flies. The growth rate of the peritrophic membrane is 1 mm./hour during the first 30 hours after emergence, and also after feeding. The distribution of the blood meal in relation to the growth of the peritrophic membrane makes it appear unlikely that the membrane itself is the barrier mechanism. A postulated adjustment period for trypanosomes in the crop of young flies (with an incomplete peritrophic membrane) is supported by cytochemical evidence concerning an enzymic transformation within 1 hour of feeding. This phenomenon implies a double transformation for successful host transfer: one (well established) in the vertebrate host sometime before transfer, a second (new) in the fly, immediately after transfer. The destruction of non-transformed trypanosomes in the mid-gut (after leaving the crop) of mature tsetse flies is considered to be the main establishment barrier.

A comparative study on the ultrastructure of plasmodium sporozoites within the oocyst and salivary glands, with particular reference to the incidence of the micropore

Abstract: 1. 1. The ultrastructure of sporozoites of 5 species of malaria parasites, Plasmodium vivax, P. cynomolgi, P. gallinaceum, P. berghei nigeriensis and P. vinckei chabaudi has been studied both in the o6cyst and the salivary gland of the mosquito. 2. 2. Micropores were readily found in both situations in P. vivax, P. cynomolgi and P. gallinaceum , but none were detected in the rodent species. 3. 3. Usually only 1 micropore was seen in the sporozoite; 2 micropores were seen in single sporozoites of P. cynomolgi , and on one occasion 6 were seen on the surface of the maturing sporoblastoid in P. vivax . 4. 4. Sections of 2,000 sporozoites were examined in each group, the incidence of the micropore was rather over 1%, though it reached 5% in sporozoites of P. cynomolgi in the salivary gland. 5. 5. There was little difference in the incidence of the micropore between the oocyst and salivary gland. 6. 6. The possible relationship between the absence of a micropore in the sporozoites of the rodent species and the well known poor infectivity of these parasites is discussed.

Isolation of arboviruses from mosquitoes, biting midges, sandflies and vertebrates collected in Queensland, 1969, and 1970.

Abstract: 30 virus strains were isolated from arthropods or vertebrates taken at 3 centres in Queensland in 1969 and 1970. They included representatives of 6 virus types distinct from any previously isolated in Australia. Prototype strains, suggested names and sources of first or repeatable isolations of the 6 viruses were: Ch9824, Charleville virus, from Phlebotomus spp. and the reptile Gehyra australis; Ch9935, Warrego virus, from Culicoides spp.; MRM10434, Mitchell River virus, from Culicoides spp.; Ch12048, Wallal virus, from Culicoides spp.; MRM13443, Wongorr virus, from Aedes lineatopennis; MRM14556, Ngaingan virus, from Culicoides brevitarsis . Mouse neutralization tests on sera from vertebrates of various species detected serum inhibitors to Warrego, Wallal and Ngaingan viruses in wallabies and kangaroos, and to Warrego, Mitchell River, Wongorr and Ngaingan viruses in cattle. These findings increase to 30 the number of viruses isolated in Australia and tentatively viewed as arboviruses, and underline the importance of biting midges and sandflies as virus vectors.

Scabies, pyoderma and nephritis in Zaria, Nigeria. A clinical and epidemiological study

Abstract: The epidemiology and clinical features of skin rashes, pyoderma, and pyoderma with nephritis in children and adults in Zaria is described. Scabies is endemic in Zaria especially among young children, and boys at the Koranic schools. Pyoderma follows secondary infection of scabies and is more prevalent towards the end of the humid rainy season in August and September. Acute glomerulo-nephritis is common at this time also. Of 20 patients with pyoderma and nephritis 16 had scabies which had become infected. Group A streptococci were isolated from the skin lesions of 11 patients, but only 2 strains—one each of types M49 and M55—recognized to be associated with nephritis, were recovered. 3 patients had an uncommon type, M26 which had not previously been suspected of causing nephritis. Serum complement was low in all 10 patients with nephritis who were tested. Anti-deoxyribonuclease B was significantly more useful as an index of streptococcal infection than the antistreptolysin 0 titre.

Cutaneous leishmaniasis in the Sudan

Abstract: The epidemiology, clinical features, pathology, immunology and treatment of cutaneous leishmaniasis in the Sudan are described. The majority of patients came from kala-azar endemic areas of the central Sudan. The aetiology of the disease is discussed. Clinically the lesions are divided into 3 types but with rare exceptions the pathological changes in all types are essentially the same. Immunoglobulins IgG and IgM are elevated in cutaneous, mucosal and visceral leishmaniasis, but IgA is only significantly increased in the mucosal type. Compared with the other forms of leishmaniasis the cutaneous disease shows the lowest levels of fluorescent antibodies. In the Sudan cutaneous leishmaniasis responds well to sodium stibogluconate (Pentostam). The results of leishmanin skin test surveys carried out in 3 different regions of the country are reported and discussed.

The differentiation of Trypanosoma rhodesiense from T. brucei by means of human serum

Abstract: 1. 1. A review is made of the Blood Incubation Infectivity Test (BIIT) introduced by Rickman and Robson (1970) to differentiate Trypanosoma rhodesiense from T. brucei in the laboratory. This test consists of incubating the trypanosomes with human blood and then injecting them into a rat; if the rat becomes infected, the trypanosomes are probably T. rhodesiense, and conversely. 2. 2. In the present paper it is shown that most of the effect of the human blood or serum is exerted after injection into the animal, and not during the previous incubation in vitro; moreover, the effect is proportional to the dose of blood per weight of animal. Accordingly, improved methods of conducting the test are recommended, especially the inoculation of the trypanosomes—blood mixture into 5 mice (rather than 1 rat), each animal to receive at least 0·4 ml. human blood per 20 g. weight. 3. 3. Further, the test should be interpreted according to statistical definitions of what is to be accepted as “serum-resistance”. Provisionally a strain which can infect 20% of the animals (treated with human blood as above) might well be regarded as “serum-resistant” (probably T. rhodesiense) and so potentially dangerous to man.

Spinal cord complications of acute schistosomiasis mansoni.

Abstract: 5 cases of clinically unsuspected involvement of the spinal cord by S. mansoni are reported. In contrast to the cases usually described in the literature, the nervous system involvement was observed during the acute phase of the infection. One of the patients exhibited a clinical picture closely resembling that of the Guillain-Barre syndrome, and cure was not dependent upon the use of corticoid hormone or antischistosomal therapy. 2 other patients improved after neurological involvement (paraparesis and paraplegia) following the completion of specific treatment (hycanthone). The sudden appearance of a polyradiculoneuritis syndrome was observed in 1 patient during treatment with niridazole. In another patient who developed a sudden transverse myelitis at T.11 with flaccid paraplegia, antischistosomal therapy apparently did not influence the course of the neurological process. It is suggested that the nervous system involvement in the reported cases cannot be explained entirely by the mechanical action of eggs and worms and the resultant granuloma formation. In the authors' opinion an anomalous response of the nervous system to the immuno-allergic products derived from dead worms and; or their eggs probably was responsible for the clinical manifestations of spinal cord involvement.

Interaction of salmonellae and schistosomes in hostparasite relations

Abstract: Salmonella paratyphi A were cultured from the tegument of Schistosoma mansoni after the worms were filtered from 2 patients with naturally occurring chronic Salmonella paratyphi A infection Examination by immunofluorescence microscopy of the S mansoni revealed S paratyphi A colonies on and within the surface tissues of the schistosomes To further define and establish this relationship a series of laboratory experiments were conducted and subsequently S paratyphi A were also cultured from the tegument of schistosomes (1) after the bacteria were incubated with the S mansoni in vitro ; and (2) following recovery of the worms from mice previously inoculated with the salmonella In addition, in the presence of S mansoni, S paratyphi A was shown to be protected from the bactericidal effects of ampicillin in vitro This bacteria-host-parasite interaction may in part explain why Salmonella paratyphi A infection and schistosomiasis clinically occur frequently together and present such a difficult therapeutic problem

Studies on the immunology and serology of leishmaniasis. IX. Serological investigation of the parasites of Indian kala-azar and Indian post-kala-azar dermal leishmaniasis.

Abstract: The antigenic constitution of 4 strains of L donovani from kala-azar and of 4 strains of the parasite from patients with post-kala-azar dermal leishmaniasis from West Bengal, India, was examined by indirect haemagglutination test performed on antigen cross-absorbed antisera Antigenically all the strains of L donovani from West Bengal, India, were essentially similar but differed from a strain of L donovani from Ethiopia

Dietary factors affecting the pathogenicity of Entamoeba histolytica in rats

Abstract: Weanling rats given protein deficient diets for 2 to 4 weeks and then infected intracaecally with Entamoeba histolytica trophozoites showed a greater susceptibility to infection compared with controls. The proportion of infected animals that developed caecal ulceration was also increased. Supplementation of the low protein diet with extra carbohydrate produced an even greater infection rate but the likelihood of caecal ulceration was lower. No relationship between amoebic infection and the bacterial flora or pH of the caecum was noted, however the redox potential was lower in those animals that developed ulceration. The possible mechanisms involved are discussed together with the relevance of these findings to human amoebiasis.