Showing papers in "Annals of Tropical Medicine and Parasitology in 1980"
TL;DR: A series of N-benzyloxydihydrotriazines were prepared and found to have antimalarial activity against Plasmodium berghei infections in mice, and one of the most active compounds is 4,6-diamino-1.
Abstract: A series of N-benzyloxydihydrotriazines were prepared and found to have antimalarial activity against Plasmodium berghei infections in mice. One of the most active of these compounds. 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(3,4 dichlorobenzyloxy)-1,3,5-triazine hydrochloride (clociguanil; BRL 50216) was selected for further evaluation.In the four day suppressive test against P. berghei in mice the ED50 of clociguanil was 0·16mg/kg and the ED90 was 0·39 mg/kg when given by the subcutaneous route. This is approximately 30 times more active than cycloguanil and ten times more active than chloroquine when compared in the same test system. In therapeutic experiments a single dose of 100 mg/kg clociguanil given by the oral or subcutaneous route completely cleared an established infection of P. berghei 72 hours after dosing. The acute LD50 in mice by the subcutaneous route was shown to be greater than 2·5 g/kg.Mode of action studies indicated that clociguanil is a dihydrofolate reductase inhibitor of Plasmodium ...
169 citations
TL;DR: The results indicate that Toxoplasma infection probably affects the animal's response to its environment and the stimulation arising from it, and may even affect endogenous regulatory processes in the brain.
Abstract: Observational methods, using video recordings and computer-assisted data analysis, were used to investigate the behaviour of Toxoplasma-infected mice. Infection had a selective effect, increasing t...
84 citations
TL;DR: For 228 of 425 deaths occurring among 26 100 people of known age in the Malumfashi area of northern Nigeria, data were collected on symptoms present prior to death, and data for the period November 1977-October 1978 have been analysed.
Abstract: Schistosomiasis is endemic in Nigeria. Schistosoma haematobium predominates in the dry, northern regions where the infection is focal and acquired in seasonal pools—there is little S. mansoni in the Malumfashi area. The degree of endemicity was much lower than expected, for research at Malumfashi followed a period of drought which produced a marked decline in S. haematobium transmission and a consequent low prevalence of medical complications. Boys were the principal group at risk and the main environmental contaminators. Screening tests of renal function showed no significant impairment in a selected group of infected males, but there were very few with serious urological lesions. Infected subjects with heavy proteinuria represented less than 1% of the population, but they had a good prognosis and responded well to metrifonate. High urinary blood and protein levels were related to intense infection and indicated lower renal tract pathology. Micturition disturbance was common but required further objectiv...
71 citations
TL;DR: Fishing, bathing, swimming and playing in water were the most important activities at the Ruwan Sanyi dam site, northern Nigeria, in terms of schistosomiasis transmission, which accounted for the marked male predominance of Schitosoma haematobium infection in Muslim communities of this area.
Abstract: Fishing, bathing, swimming and playing in water were the most important activities at the Ruwan Sanyi dam site, northern Nigeria, in terms of schistosomiasis transmission Various washing activities were important in exposure to the infection Males were responsible for 98% of activity involving contamination and exposure This accounted for the marked male predominance of Schitosoma haematobium infection in the Muslim communities of this area, where boys under the age of 21 years were responsible for more than 77% of environmental egg contamination Peak water-contact activity occurred in the afternoon and this coincided with the peak cercarial shedding period and the peak urinary egg output As a result of the construction of many such dams in this part of northern Nigeria, the recent upward trend in schistosomiasis tramission is likely to be maintained Fishing is a new and a potentially important activity in transmission Any future programme to control urinary schistosomiasis in this area should pay particular attention to this activity as well as group swimming activity by young males, who should be the prime target
70 citations
TL;DR: If Toxoplasma infections impair responsiveness to novel stimuli, then infected mice are more likely to be taken by predators, and this suggestion has important implications for the understanding of one of the major ways in which T oxoplasma passes from host to host.
Abstract: Male mice were exposed to a black arm and the stem of a Y-maze; entrance to a white arm was blocked by a transparent door. Toxoplasma-infected mice were significantly less active and tended to produce fewer faecal boluses than uninfected controls. In a subsequent free-choice trial, in which both arms were black, the uninfected mice spent significantly more time in the novel (previously blocked) arm; the infected mice showed no preference for either choice arm. Possible explanations are discussed. In particular, it seems that Toxoplasma-infected mice may be less responsive to novel stimuli. This suggestion has important implications for our understanding of one of the major ways in which Toxoplasma passes from host to host. If Toxoplasma infections impair responsiveness to novel stimuli, then infected mice are more likely to be taken by predators.
66 citations
TL;DR: Although drug activity is not enhanced as compared to free drug, a simplified experimental therapy scheme could be developed, which may facilitate comparative pharmacokinetic studies of various drug delivery systems.
Abstract: Due to a significant reduction of toxicity, 100% curative (causal prophylactic) doses of primaquine diphosphate entrapped in liposomes (60 and 70 mg/kg body weight) can be administered in a single intravenous injection to treat sporozoite-induced Plasmodium berghei infections of mice.Although drug activity is not enhanced as compared to free drug, a simplified experimental therapy scheme could be developed, which may facilitate comparative pharmacokinetic studies of various drug delivery systems.
61 citations
53 citations
TL;DR: It is recommended that quantitative methods of the clinical reaction to microfilaricides form a basic part of the assessment of any drug used in the control of onchocerciasis.
Abstract: A method of quantitation of the clinical reaction to microfilaricides has been devised at the Onchocerciasis Chemotherapeutic Research Centre at Tamale, in the savanna area of Northern Ghana. The method employs commonly occurring reactions--pruritus, rash, glandular reactions, musculoskeletal, febrile and cardiovascular--and a scoring system with a built-in weighting factor. Although the method is time-consuming and requires close, continuous observation of patients, it should permit more specific statements to be made about the severity of clinical reactions in individual patients or in groups of patients taking similar or different doses of the same drug or taking different drugs of the same drug or taking different drugs on a comparative basis. It is recommended that quantitative methods of the clinical reaction to microfilaricides form a basic part of the assessment of any drug used in the control of onchocerciasis.
53 citations
TL;DR: Motor performance in Toxoplasma-infected mice and uninfected controls was assessed by placing them, individually, on a rotating cylinder, and the infected mice fell significantly more often than the unin infected mice.
Abstract: Motor performance in Toxoplasma-infected mice and uninfected controls was assessed by placing them, individually, on a rotating cylinder. The infected mice fell significantly more often than the controls. The difference was independent of differences in fearfulness (as measured by defaecation counts) and general bodily health (as measured by body weight). Although Toxoplasmatissue cysts were present in the brains of all of the infected animals, there was no significant correlation between cyst counts (either in the cerebellum or brain minus cerebellum) and number of falls within the infected group. It is suggested that the absence of significant correlations may have been due to the restricted range and variability in tissue cyst counts.
53 citations
TL;DR: The joint blood schizontocidal action of mefloquine with the S-P combination was shown to be additive, not potentiating, and resistance to all the compounds used under these experimental conditions was shows to be unstable on withdrawal of the drug selection pressure.
Abstract: Lines of Plasmodium berghei were exposed to drug selection pressure in successive passages in mice. The compounds used were chloroquine, mefloquine, a 2:1 mixture of sulphadoxine with pyrimethamine (S-P), and a variable mixture of mefloquine with S-P. Resistance developed to all lines. Resistance to the S-P combination developed significantly more slowly than did resistance to chloroquine or mefloquine. The development of resistance to the mixture of mefloquine and S-P was greatly inhibited.The joint blood schizontocidal action of mefloquine with the S-P combination was shown to be additive, not potentiating.Resistance to all the compounds used under these experimental conditions was shown to be unstable on withdrawal of the drug selection pressure.The mefloquine-resistant line remained sensitive to chloroquine but was cross-resistant to quinine and to a synthetic quinine analogue. The line which was resistant (at a low level) to mefloquine plus S-P was sensitive to chloroquine, but was resistant to pyrim...
53 citations
TL;DR: Of 106 victims of previous spitting cobra bite, only 8·5% were treated in hospital, and physical deformity as a result of necrosis from poisoning was present in 19%.
Abstract: The spitting cobra, Naja nigricollis, is responsible for most cases of snake bite in the Malumfashi area. A survey revealed an incidence of N. nigricollis bite of 15 to 20 per 100 000 population per year in this part of northern Nigeria, with an estimated natural mortality of 5%. Of 106 victims of previous spitting cobra bite, only 8·5% were treated in hospital, and physical deformity as a result of necrosis from poisoning was present in 19%. This emphasized the fact that statistics based on hospital admissions seriously underestimate snake bite incidence, morbidity and mortality. Naja nigricollis is also important because of its ability to spit venom into the eyes of an assailant. Snake venom ophthalmia is usually regarded as having a benign course, but victims were described who had suffered more serious effects, including blindness. The epidemiology of human encounters with the spitting cobra is discussed, and it is shown that N. nigricollis is able to maintain a close association with man. The cobra i...
TL;DR: Two methods for investigating the action of drugs against a viscerotropic Leishmania in mice were described and Pentamidine and diminazene aceturate proved to have a slow action which was more readily demonstrated if the observation period was prolonged.
Abstract: A description is given of two methods for investigating the action of drugs against a viscerotropic Leishmania in mice. The parasite employed was isolated from a patient with kala-azar in Ethiopia. It is designated 'L. infantum LV9' and produces a visceral infection in NMRI mice. The biochemical typing characters of the parasite are described. In Method A, infected animals were treated from the 5th or 6th day after infection (D + 5 or D + 6) for five consecutive days. They were sacrificed 24 hours after the completion of drug treatment and an estimate was made of the amastigote load in the liver. A comparison of this with untreated controls gives an index of activity of a test drug, from 0 to 3. Method B is similar except that the ED50 and ED90 are determined by graphic analysis of data from graded drug doses. A comparison is made with sodium stibogluconate used as a positive drug control to yield a 'Pentostam Index'. The course of infection in BALB/c and NMRI mice is compared with that in random-bred Swiss mice in which 'L. infantum LV9' produces an inconsistent infection. An inoculum of 10(7) amastigotes produces a peak parasite intensity between D + 15 and D + 20. The ED50 and ED90 of sodium stibogluconate (Pentostam) (as Sbv) in Method B are 22 x 5 and 46 x 5 mg/kg sc daily x 5. (By Method A the single dose figures are 65 and 280 mg/kg.) For routine use a standard dose level of 120 mg/kg sc daily x 5 of Pentostam (Sbv) is used in Method B. The ED50 and ED90 of meglumine antimoniate (Glucantime) (as Sbv) in Method B are 11 x 6 and 66 x 7 mg/kg sc daily x 5. Data are given for other antimonials in Method A. Pentamidine and diminazene aceturate proved to have a slow action which was more readily demonstrated if the observation period was prolonged. Amphotericin B was moderately active but toxic to the host. The relevance of these models and a comparison of data found in the mouse and hamster are debated.
TL;DR: Tissue reactions in snails with self-cure demonstrate involvement of two types of cells, granulocytes and hyalinocyte-like cells; formation of amoeba-fibrous capsules; limited tendency of granulocyte to become attracted to the parasites; slow process of parasite destruction; and a possible involvement of humoral factors.
Abstract: In Biomphalaria glabrata with a strong natural resistance, Schistosoma mansoni sporocysts are rapidly encapsulated by granulocytes and killed, mainly by the strong phagocytic activity of the cells. Irradiated Echinostoma paraensei sporocysts seem able to suppress the function of the granulocytes.Tissue reactions in snails with self-cure demonstrate: involvement of two types of cells, granulocytes and hyalinocyte-like cells; formation of amoebo-fibrous capsules; limited tendency of granulocytes to become attracted to the parasites; a slow process of parasite destruction; and a possible involvement of humoral factors. It seems that there is partial suppression of the granulocyte function in snails with self-cure.
TL;DR: The prevalence of infection with hydatid cysts in sheep, goats, cattle and camels slaughtered at Baghdad Abattoir was recorded over a period of 18 months and the fertility rate of the cysts was higher in camels than in sheep or goats.
Abstract: The prevalence of infection with hydatid cysts in sheep, goats, cattle and camels slaughtered at Baghdad Abattoir was recorded over a period of 18 months. The infection rates were generally lower than had been reported in previous surveys but remained high in camels. The lower prevalence rates were attributed to the destruction of stray dogs, improved standards of meat inspection and an overall improvements in socio-economic conditions. The fertility rate of the cysts was higher in camels than in sheep or goats. All the cattle cysts were sterile.
TL;DR: It is suggested that C. nubeculosus can act as a vector of BTV when simultaneously infected with virus and the microfilariae of a filarial worm.
Abstract: Culicoides nubeculosus under normal experimental conditions was found incapable of supporting multiplication of bluetongue virus (BTV) after infection via the oral route. Simultaneous infection with BTV and the microfilariae of Onchocerca cervicalis, a filarial worm of the horse, transformed this situation. A small proportion of infected midges subsequently developed high titres of virus, which persisted until the termination of the experiment at day 13 post infection. C. nubeculosus intrathoracically inoculated with BTV were found to transmit the virus after 7, 8 and 14 days incubation at 26°C, with no evidence for a ‘salivary gland barrier’. It is therefore suggested that C. nubeculosus can act as a vector of BTV when simultaneously infected with virus and the microfilariae of a filarial worm.
TL;DR: Histological studies showed that small lymphocytes were always present but plasma cells never formed a prominent component of the inflammatory response, and 15 out of 16 cases skin-tested with leishmanin demonstrated strongly positive delayed type hypersensitivity.
Abstract: Eighteen leishmaniasis cases were diagnosed as lupoid because the duration of their disease varied from 1·5 to eight years and the diameter of the lesion varied from 1 cm to 6 cm. In smears prepared from exudates of the lesions amastigotes were observed only once. No organisms were recovered in cultures from biopsy material from eight cases. Histological studies showed that small lymphocytes were always present but plasma cells never formed a prominent component of the inflammatory response. Histiocytic granulomas, with or without giant cells, were seen. No acid-fast organisms were demonstrated. Fifteen out of 16 cases skin-tested with leishmanin demonstrated strongly positive delayed type hypersensitivity. However, when these 15 patients were skin tested with PPD only three showed positive skin reactivity. Only four patients had IFAT antibody titres in excess of 1 /32.
TL;DR: Two out of 288 sick and emaciated dogs from homesteads in the Machakos District of Kenya, where human kala-azar cases existed, were found to be infected with leishmaniasis.
Abstract: Two out of 288 sick and emaciated dogs from homesteads in the Machakos District of Kenya, where human kala-azar cases existed, were found to be infected with leishmaniasis. The leishmanial strain isolated from one of the dogs was characterized enzymologically and serologically and found to be identical with strains isolated from human kala-azar cases and Phlebotomus martini. The significance of these findings is discussed in terms of the general epidemiology of visceral leishmaniasis in Kenya.
TL;DR: In this region of Uganda, there was continuous transmission of pathogenic trypanosomes by the three tsetse species among their natural hosts; when present, the vectors' adventitious hosts became exposed to a high risk from the diseases.
Abstract: Glossina pallidipes, G.f. fuscipes and G. brevipalpis in Stages I and II of hunger were caught from Bukunya and Buyundo villages in south-east Uganda during the period December 1969 to February 1971, and the origins of their blood meals identified. G. pallidipes fed mainly on bovids in the two villages; bushbuck was the most favoured host (44·9% of all blood feeds) though in Buyundo buffalo provided a significant alternative (20·8%). G.f. fuscipes frequently fed on bovids (75·6%), particularly bushbuck (46·7%), but it had a wider range of acceptable hosts. In both villages, G. brevipalpis took most of its blood meals from bushpig (45·5%), bovids (25·6%) and hippopotamus (28·5%). The feeding patterns of the three tsetse species during different months of the study period showed only small variations, and such differences were due probably to variations in the availability of the hosts.Examination of the relationships between trypanosome infection rates and natural hosts of the three vector species showed t...
TL;DR: In this paper, two models have been established of leishmanial infections in random-bred TFW albino mice, one with Leishmania major LV39 and the other with L. mexicana amazonensis LV38.
Abstract: Two models have been established of leishmanial infections in random-bred TFW albino mice, one with Leishmania major LV39 and the other with L. mexicana amazonensis LV38. These parasites produce consistent lesions when injected subcutaneously a short distance anterior to the base of the tail. Consistent infections could not be produced in the mice with other lines of the L. mexicana group of skin-dwelling protozoa, nor with a line of L. braziliensis guyanensis (LV475). The development of procedures for the maintenance of these parasites, the routine infection of mice and drug testing are described. L. major inocula consist of 1--5 X 10(6) promastigotes derived from NNN culture. L. m. amazonensis inocula contain approximately 10(7) amastigotes obtained from lesions in hamsters. The effects of drugs on the rodent lesions are assessed by two methods. Method A provides a simple lesion score from 0 to 3 made when lesions in control animals begin to reach maximum development (about six weeks after infection). Method B summates earlier 'mean lesion scores' to provide a graphic analysis of doses giving 50 and 90% lesion suppression at the end of seven weeks after the start of treatment which is for five consecutive days (SD 50 and SD90). The activities of several compounds used for the treatment of human leishmanial infections (organic antimonials, diamidines, amphotericin B and primaquine) are compared in mice infected with L. major LV39, L. m. amazonensis LV78 and 'L. infantum LV9' (the latter as reported earlier). It is concluded that the rodent models provide a good parallel with the response to these compounds in man. The visceral organism is significantly more responsive to Pentostam and Glucantime than are L. major or L. m. amazonensis. Primaquine is active only against 'L. infantum LV9'. All three parasites in mice respond to Berenil, but not to pentamidine which is used in the treatment of kala-azar. Amphotericin B is effective against cutaneous and visceral infections, but precautions must be taken to ensure its absorption by experimental animals.
TL;DR: More oocysts of Plasmodium yoelii developed in Anopheles stephensi if the mosquitoes received a supplement of p-aminobenzoic acid in their diet prior to their taking an infective blood meal, than in unsupplemented control insects.
Abstract: More oocysts of Plasmodium yoelii developed in Anopheles stephensi if the mosquitoes received a supplement of p-aminobenzoic acid (PABA) in their diet prior to their taking an infective blood meal, than in unsupplemented control insects. The optimum concentration was 0.05% PABA in 10% sucrose. This effect was not observed if the blood meal was taken prior to feeding with PABA. Similarly, PABA administered to gametocyte-carrying mice increased the numbers of oocysts developing in mosquitoes fed on them subsequently, the effect also being dose dependent, and not mediated through an increase in gametocyte numbers. Sulphadoxine (which blocks PABA uptake) had the opposite action, reducing the numbers of oocysts either when fed directly to the mosquitoes or to the donor mice. These results are compared with those reported in other host-parasite systems by earlier workers, and certain paradoxical observations are discussed with reference to a possible relationship between sulphonamides and contaminating microorganisms in the vector mosquitoes.
TL;DR: Ixodes trianguliceps is possibly the only species of tick which infests small mammals in the areas studied, and the occurrence of Babesia microti as a zoonotic infection is discussed.
Abstract: Ixodes trianguliceps is possibly the only species of tick which infests small mammals in the areas studied. The tick has two distinct peaks of activity, in July and October, with somewhat lower infestations in the intervening months; no activity is apparent during the winter. The seasonal activity is triggered by rising spring temperatures which activate the overwintering stages to complete the life cycle. Ixodes trianguliceps is possibly a non-nidicolous species that develops close to the nest of the host; copulation and fertilization may occur on the host.Babesia microti (Knowsley strain) is principally a parasite of microtine rodents and is transmitted in nature through the larval/nymphal instars of Ixodes trianguliceps. The protozoan parasite spends far more time in the vector than in the vertebrate host and is carried over from one season to another in the tick. The occurrence of Babesia microti as a zoonotic infection is discussed.
TL;DR: It is concluded that DEC is more effective than metrifonate and remains the 'reference' microfilaricide although its effects are more severe than those of metr ifonate.
Abstract: In a single-blind comparative study of diethylcarbamazine (DEC) and metrifonate against onchocerciasis, 20 patients received a total dose of 6·6 g DEC over a two-week period and 20 patients each received one dose of metrifonate 10 mg/kg body weight at ten-day intervals, three times. Both the efficacy and the severity of reaction to treatment were measured. DEC proved the more effective, destroying 98·9% of the microfilarial load while metrifonate destroyed only 75·4% (assessed one week after completion of treatment). The reaction to treatment was much more severe in patients treated with DEC. The persistence of significant postural cardiovascular effects for two weeks after the completion of DEC needs to be considered in mass therapy. The pattern of re-emergence of skin microfilariae indicated no difference between the two drugs over a six-month period.It is concluded that DEC is more effective than metrifonate and remains the ‘reference’ microfilaricide although its effects are more severe than those of ...
TL;DR: Both intestinal and urinary schistosomiasis occur widely in Saudi Arabia and the examination of different types of water bodies did not show any apparent overlap between the different snail vectors of Schistosoma.
Abstract: Both intestinal and urinary schistosomiasis occur widely in Saudi Arabia. The rate of snail infection with schistosome cercariae was highest in Gizan. The intermediate host for Schistosoma mansoni is Biomphalaria arabica and for S. haematobium, Bulinus beccarii (and possibly Physa acuta, which was recorded for the first time in the central region of Saudi Arabia). The examination of different types of water bodies did not show any apparent overlap between the different snail vectors of Schistosoma.
TL;DR: Two methods were used to examine a variety of compounds for possible activity against a viscerotropic infection of ‘Leishmania infantum LV9’ in NMRI mice, and only two 6-aminoquinolines were fully active, but they were also toxic to the host.
Abstract: Two methods were used to examine a variety of compounds for possible activity against a viscerotropic infection of ‘Leishmania infantum LV9’ in NMRI mice. The parasite originated from a human case of kala-azar in Ethiopia. The procedures followed were described in detail in the previous papers in this series.Little activity was detected in a number of sulphonamides, dihydrofolate reductase inhibitors, antimalarials, schistosomicides, trypanocides, or antibiotics by these methods. Only cycloguanil HCl and primaquine phosphate among the antimalarials showed marked activity. Racemic 2-dehydroemetine and amphotericin B were moderately active. Pentamidine and diminazene aceturate in this model were marginally active only.Among 46 chemical structures (selected partly on the basis of interesting activity against Leishmania discovered earlier in tissue culture) only two 6-aminoquinolines were fully active, but they were also toxic to the host. Good activity was displayed by two metronidazole analogues, and one th...
TL;DR: Using biochemical and ultrastructural parameters, seven strains of Endotrypanum were divided into two taxonomic units, however, this separation does not agree with the original identification of the stocks as either E. schaudinni or E. monterogeii.
Abstract: Using biochemical and ultrastructural parameters, seven strains of Endotrypanum were divided into two taxonomic units. However, this separation does not agree with the original identification of the stocks as either E. schaudinni or E. monterogeii. Clusters of discrete particles, 40–80 nm diameter, variable in shape and with a 14–18 nm thick electron-dense wall were observed in four of the stocks. One stock, isolated from a sandfly, Lutzomyia trapidoi, was identified as an Endotrypanum sp.
TL;DR: There was a relationship between wind speed and catches of Anopheles melas and Culex thalassius which attempted to bite man at ground level and on an open scaffolding tower, in cleared bush in The Gambia.
Abstract: There was a relationship between wind speed and catches of Anopheles melas and Culex thalassius which attempted to bite man at ground level and at 4 and 8 m on an open scaffolding tower, in cleared bush in The Gambia. It was expected that in winds which exceeded their flight speed, no mosquitoes would be able to approach and attack men on the tower. Catches of mosquitoes fell off sharply in winds of 120 cm/s, which may approximate to their flight speed, although some insects were still captured at the highest wind speeds encountered.