Human cysticercosis: parasitology, pathology, clinical manifestations and available treatment.

Human cysticercosis is a global health problem and neurocysticercosis a serious clinical syndrome. The diagnosis of neurocysticercosis can now be made with a high degree of accuracy by scrutiny of clinical signs and symptoms in combination with X-ray, computed tomography or magnetic resonance imaging, serological tests and laboratory examinations. Differential clinical diagnosis with tumor, and vascular and inflammatory conditions, may however, prove difficult in nonendemic areas. The management of cysticercosis has been radically changed by the advent of effective chemotherapy. Both the heterocyclic pyrazinoisoquinoline compound, praziquantel and the benzimidazole carbamate, albendazole, have now been extensively tested and successfully used for treatments of neurocysticercosis, usually in combination with corticosteroids. The definition of appropriate criteria and guidelines for the use of chemotherapy, may however, require further research. Surgical interventions continue to play an important role in certain clinical presentations. Recent advances in immunological research hold realistic promise for the development of a vaccine against Taenia solium.

Progress in the control of schistosomiasis in Egypt 1985-1988.

Continuing epidemiological evaluation of schistosomiasis intervention measures applied in Middle and Upper Egypt since 1985 indicate that a large measure of control of Schistosoma haematobium has been achieved in relation to both prevalence and intensity of the infection and incidence of new infections. Transmission control has, however, been inadequate in many areas, since numerous re-infections occurred in treated schoolchildren. Variable compliance rates in the chemotherapy delivery system were probably, in part, an important contributory factor, and short-comings of the selective and/or focal mollusciciding strategy were also probably responsible for many new cases and re-infections. Chemotherapy delivery has now been improved following the introduction of single dose treatments with praziquantel and it is expected that there will be an increased demand for treatment following the introduction of a new information-education-communication campaign. In communities with geometric mean egg-output of less than 50 per 10 ml of urine, acceptable control of the potential for development of schistosomal disease can be expected. It is concluded, therefore, that the future maintenance control strategy in this project area may call for more frequent chemotherapy treatments in identified foci of high prevalence and intensity, with complementary focal mollusciciding and/or targeted treatment of schoolchildren, in order to prevent the serious consequences of infection. In 1988 the annual cost of schistosomiasis control measures per person throughout the project area (2 million irrigated feddans (c .800,000 hectares] containing 12 million people) was 0.5 Egyptian pounds (LE) (US$ 0.20), representing 5.2% of the annual expenditure per person in Egypt (LE 9.6) for all health services.

Antibody is responsible for the passive transfer of immunity to mice from rabbits, rats or mice vaccinated with attenuated Schistosoma japonicum cercariae.

Sera from rabbits, rats and mice multiply-vaccinated with attenuated cercariae of Schistosoma japonicum conferred high levels of resistance against challenge to naive recipient mice (up to 97, 64 and 60% respectively). Vaccinated rabbit and rat sera were given before challenge and vaccinated mouse serum 5 days after challenge. To show that the protective factors in these sera were antibodies, vaccinated rabbit and mouse sera were fractionated by protein A-Sepharose and the fractions precipitated by 50% ammonium sulphate. The protein A-Sepharose binding or non-binding fractions in vaccinated rabbit serum transferred approximately equal levels of significant resistance to mice, suggesting that both the IgG and non-IgG components of vaccinated rabbit serum are protective. The major part of the protective activity in vaccinated mouse serum was transferred to recipients by the protein A-Sepharose binding fraction, i.e. the IgG antibodies. Heat inactivation of sera at 56 degrees C for 3 h affected the protective capacity of vaccinated rat sera, but not that of vaccinated rabbit or mouse sera.

Immunization of baboons with attenuated schistosomula of Schistosoma haematobium: levels of protection induced by immunization with larvae irradiated with 20 and 60 krad.

We have shown previously that baboons (Papio anubis) develop high levels (greater than 80%) of protection against challenge infection following immunization with Schistosoma haematobium cercariae irradiated with 20 krad. In the present study baboons were immunized with schistosomula irradiated with either 20 krad or 60 krad, with variations in the timing and number of larvae comprising each vaccination. Baboons immunized 2 or 3 times with schistosomula irradiated with 20 krad were significantly more protected (85-90%) against challenge infection than baboons similarly immunized with larvae receiving 60 krad (56-50% protection). Baboons immunized with schistosomula irradiated with 20 krad were better protected against challenge infection at 8 weeks after immunization than at 28 weeks after immunization. Protection was manifest by a reduction in worm numbers, tissue and excreta egg counts, gross pathology and, to a lesser extent, by stability of body weight and haematological indices following challenge. Enzyme-linked immunosorbent assay (ELISA) results of selected baboon sera showed few differences related to irradiation dose alone, but titres were higher in baboons receiving booster immunizations, and there was a significant correlation between titres immediately preceding challenge and the degree of resistance. Examination of responses to individual schistosomular surface antigens by immunoprecipitation and sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed no correlation between the pattern of antigens recognized and resistance status. As with the ELISA assay, an anamnestic response was detected after vaccination, while the amount of antibody present declined markedly with increasing time after individual immunizations.

Cross protection between a laboratory passaged Chinese strain of Schistosoma japonicum and field isolates of S. japonicum from China.

Our laboratory strain of Schistosoma japonicum has been isolated for 51 years, but is comparable to the indigenous Chinese parasite in terms of its infectivity to both the intermediate and definitive hosts. Vaccination with our strain protects mice against challenge with wild isolates of S. japonicum from China. Thus any defined antigen vaccine developed using our laboratory strain would be expected to protect against S. japonicum in the field in China.

Pathology resulting from the administration of a live attenuated anti-Schistosoma haematobium vaccine in baboons.

Baboons (Papio anubis) were injected in the leg muscle with 18,000 20 Krad irradiated schistosomula of Schistosoma haematobium. Four protocols were followed: single, primary injection; single injection into animals primed by patent S. haematobium infection; secondary vaccine injection following an earlier injection; and single injection following praziquantel treatment of infected animals. Injection of the putative vaccine elicited localized mixed inflammatory infiltration at the site of injection which was both intense and prolonged. Three grades of tissue reaction were seen: the relatively mild primary response; the response in infected animals which had enhanced tissue eosinophilia; and the response in animals primed by prior injection and drug-treated prior infection. The latter 2 showed intensification of eosinophilia, stellate abscesses in the lesion centers, and perischistosomular Hoeppli precipitates. Intramuscular lesions peaked at 14 days for the primary response and at 7 days for all secondary responses. Traces of the milder lesions persisted beyond 4 weeks; more severe reactions healed more rapidly. Some schistosomula survived for 14 days in the milder reactions. A few larvae were deposited in the skin by backflushing of the injectate which produced local inflammation. Compared to mice, live schistosome vaccines injected into baboons elicited greater local inflammation; however, while evidence suggested that sporadic vaccine schistosomula did reach the lymphatic nodes draining the injection sites, no systemic lesions were found and the injection sites healed in approximately 5-6 weeks without permanent damage.

Focal, seasonal and behavioural patterns of infection and transmission of Schistosoma haematobium in a farming village at the Volta Lake, Ghana.

Integrated sampling for human prevalence, intensity, and incidence of Schistosoma haematobium, as well as for human water contact and snail distribution and density was carried out in the Volta lake farming village of Agbenoxoe at various times between 1978 and 1980. Nuclepore filters were used for determining egg output. Snail sampling was by the man-time method. A new system of recording human water contact was introduced for the peculiar condition at Agbenoxoe. Results indicated significant focality of infection and transmission in the compact village, concentration in the 5- to 19-year-old age group, and distinct seasonality of transmission. Water contact was frequent but of short duration. Only a few children under the age of 5 entered the water, and age-specific curves for duration of water contact paralleled the curve for geometric mean of egg counts (log10 of eggs + 1) for males and the prevalence curve for females. Water contact for males was of longer duration than for females and included more time playing and wading. These activities probably accounted for the much higher incidence and prevalence rates recorded for males over females in the village. The concentration of infection, transmission, and water contact in the 5- to 19-year-old age groups at Agbenoxoe and villages like it supports a control strategy of treating only this age span with drugs.

Passive transfer of resistance to mice with sera from rabbits, rats or mice vaccinated with ultraviolet-attenuated cercariae of Schistosoma japonicum.

All serum transfers from donor rats or rabbits given single or multiple vaccinations of ultraviolet (u.v.)-attenuated Schistosoma japonicum cercariae conferred significant resistance against challenge to mice. Donors given 5 vaccinations, however, produced the most effective sera; rat sera giving up to 88% protection and rabbit sera up to 80%. This protective effect was species-specific and titratable. Sera from vaccinated rabbits and rats were were most effective when transferred to mice 2 h before challenge, but became progressively less effective when transferred with increasing time after challenge. These sera had no efficacy when given 6 days after challenge. Thus, sera from vaccinated rabbits and rats were effective against the early stage of migration, but did not necessarily have to act in the skin as all serum transfers were as effective against intraperitoneal as percutaneous challenge. By contrast, serum from multiply vaccinated mice had little or no protective effect when transferred to mice before challenge, but conferred 62% resistance when transferred 5 days after challenge. Further, there was an additive protective effect when vaccinated rat and mouse sera were given in combination at their optimum transfer times (days 0 and +5, respectively). Thus, there appears to be a stage-specific immune response induced by vaccination depending upon whether the vaccinated hosts are truly permissive or not. Vaccinated rats and rabbits respond to the early phase of migration and vaccinated mice make protective responses against the lung phase of migration.

The involvement of eggs and soluble egg antigens in resistance to Schistosoma japonicum.

Mice presensitized with SEA and subsequently injected with S. japonicum eggs into their lungs or liver developed pathology similar to that found in infected mice and were consequently resistant to challenge (average 33% and 53%, respectively). However, soluble egg antigens were also capable of inducing low levels of resistance in mice (average 22.5%), but intact eggs alone injected into the lungs, liver or subcutaneous tissues were not. Thus, prior sensitization to 'marginally' protective soluble egg antigens is necessary for egg induced resistance.

The induction of species-specific immunity against Schistosoma japonicum by exposure of rats to ultra-violet attenuated cercariae.

Single percutaneous immunizations of Fischer rats with 1000 ultra-violet attenuated Schistosoma japonicum cercariae induced 52-88% resistance to challenge 4 weeks later. Increasing this to 3 immunizations induced 90% resistance to challenge, and this level of protection remained undiminished for up to 40 weeks after vaccination. Rats vaccinated with gamma-irradiated S. mansoni cercariae were resistant to challenge with S. mansoni but not S. japonicum. Similarly rats vaccinated with u.v.-attenuated S. japonicum cercariae were not resistant to heterologous challenge. Thus irradiated vaccines are species-specific in both permissive and non-permissive hosts.

Evidence for an immune-dependent action of praziquantel on Schistosoma mansoni in mice.

Effective schistosomicidal action of praziquantel against Schistosoma mansoni infections in mice appears to be dependent to some extent on appropriate immunological stimulation. Indirect evidence consistent with this hypothesis was obtained by demonstrating a positive relationship between drug efficacy and both the intensity and the age of the parasitic infection. More directly, it has previously been shown that praziquantel kills fewer S. mansoni worms in immunosuppressed T cell-deprived mice than in immunologically intact controls; and we show here that infections 5 weeks old, against which the drug alone is sub-optimally active, are more effectively killed by a combination of drug and a rabbit antiserum raised against adult worm antigens.

Parasitological evaluation of curative and subcurative doses of 9-acridanone-hydrazone drugs against Schistosoma mansoni in baboons, and observations on changes in serum levels of anti-egg antibodies detected by ELISA.

Derivatives in the class of 9-acridanone-hydrazones were found to be highly active against Schistosoma mansoni in baboons. Single doses of 25 mg/kg were fully effective. Data are presented showing changes detected by ELISA in antibody levels against schistosome eggs which correlated positively with the effect of chemotherapy. This approach may help to evaluate the effects of treatment of human schistosomiasis where the detection of low egg counts is problematic.

Loss of resistance to reinfection with Schistosoma japonicum in mice after treatment with praziquantel.

Seven-week-old adult Schistosoma japonicum worms were eliminated from mice within one week of treatment with praziquantel and oviposition ceased within 2 days. The excretion of faecal eggs ceased within 2 weeks of treatment. The numbers of eggs retained in the intestine and those in the liver remained constant for up to 20 weeks after cure. Untreated, infected mice were on average 80% resistant to reinfection and mice challenged one week after treatment were equally resistant. However, reductions in the ability of mice to resist a challenge were evident as early as 2 weeks after cure (average resistance 40%) and by 5 weeks the resistance had dropped significantly (average resistance 30%) in all experiments. Mice were no longer significantly resistant to challenge 13 weeks after treatment, in 2 out of 3 experiments. It is suggested that the reduced ability of cured mice to resist reinfection is related to the resolution of the granuloma response and associated pathology rather than the loss of tissue eggs.

The simple laboratory maintenance of a highly productive Schistosoma japonicum life cycle.

The maintenance and infection of Oncomelania hupensis hupensis, the intermediate host of the Chinese strain of Schistosoma japonicum, is described. 60% of the snails exposed to miracidia became patent, and 5000 patent snails can be produced which yield over 250,000 cercariae per week. The maintenance and infection of snails require less than 8 man-hours per week.