Active Schistosomiasis Research Articles

Immunoglobulins in Human Schistosomiasis Mansoni

Immunoglobulin levels were determined by the reverse immunodiffusion technique in 3 groups of subjects: (A) 20 patients at the early stage of schistosomiasis mansoni infection; (B) 20 patients at the chronic stage of schistosomiasis; (C) 20 healthy controls. Group A showed significant increase of serum IgG (2,731 ? 608 mg/100 ml) and IgM (144 ? 92 mg/100 ml). The mean immunoglobulin levels in group C (control) were: IgG: 1,437 ? 224 mg/100 ml; IgM: 89 ? 16 mg/100 ml; IgA: 222 ? 93 mg/100 ml. The mean value of IgG, IgA, and IgM in group B did not differ significantly from the control group (1,705 317 mg/100 ml, 223 ? 120 mg/100 ml, 97 ? 15 mg/100 ml, respectively). The reverse immunodiffusion technique proved to be a simple and reliable method for the quantitative measurement of serum immunoglobulins. Human schistosomiasis mansoni presents different clinical and laboratory aspects according to the stage of the infection. During the early stage, high blood eosinophilia and positive precipitin tests are more frequent than in the chronic stage (Fiorillo et al., 1955; Ferreira et al., 1966; Reis et al., 1970). At the chronic stage (hepatointestinal and hepatosplenic forms) schistosome patients present blood eosinophilia and negative precipitin reaction (Dodin et al., 1966). Immunoelectrophoresis of sera from patients during the chronic stage shows specific antibodies against schistosome antigens in the IgG and IgM immunoglobulins (Silva and Ferri, 1965a, b). Hillyer (1969), using the conventional immunoplate technique, found increases of IgG and IgM in chronic schistosome patients. In this paper the immunoglobulin levels at the early and chronic stages of schistosomiasis were determined and an economical and very simple technique for quantitation of serum immunoglobulin is described. MATERIALS AND METHODS Schistosome patients and control Group A: Sera of 20 patients in the early stage (31 to 75 days of infection) of active schistosomiasis mansoni. Clinical diagnosis was based on the evidence provided by epidemiological data, clinical Received for publication 20 May 1970. * This work was supported by grants from the WHO, Geneva, Switzerland, and the Research Office of the U. S. Army (DAHC 19-69-G-0021). Contribution number 9 from the Schistosomiasis Research Unit. Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais. t Address: C. Postal 1404. Belo Horizonte, Brazil. symptoms, and laboratory tests as published elsewhere (Ferreira et al., 1966). All patients passed eggs in the stools, within 7 to 8 weeks after expo-

Treatment of chronic urinary salmonella carriers

Treatment of chronic urinary salmonella carriers with chloramphenicol at a dosage of 50 mg. per kg. body weight for 14 days was unsuccessful in 15 patients. All began to excrete salmonella again soon after completing treatment. All had active urinary schistosomiasis. A second group of 14 patients were treated with antimony tartrate or niridazole at a standard dose and 4 weeks of ampicillin at a dosage of 100 mg. per kg. body weight per day. 5 of these 14 patients relapsed but intravenous pyelography revealed that 3 of these 5 patients had advanced irreparably damaged urinary tracts and micturating cystograms showed that the other 2 had an established vesico-ureteric reflux. Though all 26 patients had a urinary carrier history of 12 months before treatment, all had positive blood cultures for the same organisms. It is suggested that chronic urinary salmonella carriers in Egypt be thoroughly examined and those with damaged urinary tracts due to schistosomiasis be given the benefit of anti-schistosomal treatment. Further studies are necessary to determine the exact place of prolonged chloramphenicol or ampicillin given alone or with anti-schistosomal treatment in the management of these patients.

The schistosomal circumoval precipitin test in cases of chronic prostatitis

15 patients with active urinary schistosomiasis and chronic prostatitis were studied by the COPT with regard to the antigenic power of the prostate. 12 showed positive results (weak) in prostatic fluid; all had positive sera. The titre in the serum of the schistosomiasis patients was much higher than in the prostatic fluid. 15 patients previously successfully treated for urinary schistosomiasis and 20 men with bacterial prostatitis were similarly studied; all were negative.

Immunoprecipitins in Schistosoma mansoni infections : IV. Human infections

Sera from six acute and sixty-five chronic infections of humans with active schistosomiasis have been analyzed for the presence of precipitins to S. mansoni somatic antigens. Sera from acute cases gave stronger precipitin lines to cercarial, adult worm, and egg extracts than did sera of the chronic cases. All sera reacted against at least one antigenic extract. Immunoelectrophoretic analyses of the sera revealed increases of serum IgC and serum IgM. By simple radial diffusion these are shown to be approximately 1.5 times that of normal controls. Following fractionation of these sera the precipitin response is found in two fractions differing in molecular weight and believed to correspond to serum IgG and serum IgM.

Preliminary clinical trials with hycanthone, a new antischistosomal agent.

Summary From Miracil D® (lucanthone), a hydroxymethyl derivative (hycanthone), can be obtained through the biological activity of the microorganism spergillus sclerotiorum. This compound was claimed to be the antischistosomal metabolite of Miracil D and was found very active when administered to mice, hamsters, and Cebus monkeys experimentally infected with Schistosoma mansoni. Clinical trials with hycanthone were performed on 52 patients with active schistosomiasis mansoni. The drug was administered, per os, at the dosage levels of 2 and 3 mg per kg per day with an antacid preparation, twice a day, for 5 consecutive days. In all but two patients treatment could be completed. Nausea, vomiting, anorexia, vertigo, and headache were the commonest side-effects. Therapeutic activity could be evaluated in 44 cases by repeated stool examination (four to six) or by one rectal biopsy performed at least 4 months after treatment, or by both. The percentages of patients considered as cured were 83.3 and 80.0 for the schedules of 2 and 3 mg per kg, respectively. Laboratory and clinical data on the antischistosomal activity of hycanthone obtained so far emphasize the need for further clinical trials with this compound.

Ensaio laboratorial e clínico com Hycanthone, nôvo agente esquistossomicida

A partir do Miracil D, um derivado hidroximetílico (Hycanthone) pode ser obtido através da atividade biológica do Aspergillus sclerotiorum. Êste derivado mostrou-se muito ativo quando administrado a camundongos, hamsters e macacos Cebus experimentalmente infectados com Schistosoma mansoni. Ensaios clínicos com o Hycanthone foram feitos em 52 pacientes com esquistossomose mansoni ativa. A droga foi administrada, nas doses de 2 e 3 mg/kg/ dia, junto com um anti-ácido, duas vêzes ao dia, durante 5 dias consecutivos. Com exceção de 2 casos, todos os pacientes completaram o tratamento. Náusea e/ou vômito, anorexia, tonturas e cefaléia foram os efeitos colaterais mais comuns. Atividade terapêutica foi avaliada através de repetidos exames de fezes (4 a 6) e uma biópsia retal realizada a partir do 4.° mês após o tratamento. As percentagens de cura foram de 83,3 e 80,0% com o esquema de 2 e 3 mg/kg, respectivamente. Os dados laboratoriais e clínicos sôbre a atividade esquistossomicida do Hycanthone até agora obtidos mostram a necessidade de novos ensaios com êste promissor medicamento.

The Intradermal Test in the Diagnosis of Schistosomiasis mansoni. IX. Skin Response to a Purified Fraction Isolated from Cercarial Extracts

Butanol powder from lyophilized cercariae (Schistosoma mansoni) was extracted either with 0.9 NaCI or 0.1 M borate buffer pH 8.0, precipitated at pH 4.7 and the supernatant (total extract) fractionated by column chromatography (DEAE-Sephadex). The fractions obtained were assayed for protein and polysaccharide and skin tested in patients with active schistosomiasis mansoni. Several fractions were found to elicit a skin response. One of them (fraction D, in which no polysaccharide was detected) was at least five times more active than the total extract and contained only 20% of the absorbing material at 280 mu. The skin test is a useful and practical tool for diagnosis and epidemiological surveys of schistosomiasis (Kagan and Pellegrino, 1961). However, only crude extracts or incompletely purified antigens from cercariae or adult schistosomes have been used for this test. Maximum advantage would be realized with the use of purified and chemically defined antigens. In the course of a study aiming at the purification and characterization of antigenic, enzymatic, and biologically active components extracted from cercariae of S. mansoni, several fractions were obtained. This paper presents the results of skin tests performed with fractions obtained from column chromatography on DEAE-Sephadex. MATERIAL AND METHODS Cercarial extracts from lyophilized cercariae Large numbers of Australorbis glabratus infected with S. mansoni (200 to 500 snails) were isolated in small volumes of water under conditions favoring the emergence of cercariae. The heavy cercarial suspension was sedimented overnight in conical flasks in the cold room at 5 C. The supernatant was carefully aspirated and the packed cercariae washed twice with distilled water, and then transferred to glass ampules and shell frozen at -70 C. Lyophilized cercariae were extracted with dry n-butanol at 0 C for about 20 min with continuous stirring (5 ml of butanol/100 mg of cercariae), and the extract separated by centrifugation. The residual material was reextracted with dry butanol Received for publication 1 March 1965. * This work was supported by grants from the Research Office of the U. S. Army, the WHO, the Rockefeller Foundation, and the Conselho Nacional de Pesquisas. 753 as before and with dry acetone at 15 C. The organic solvents of the precipitated material were evaporated under vacuum over CaC12. The butanol powder was then extracted twice either with 0.9% NaCl or 0.1 M sodium borate, pH 8.0, for periods of 2 hr with continuous stirring at 0 C. Some extracts were precipitated at pH 4.7 with 0.2 M HC1 according to Melcher (1943). The 10,000-g supernatant (total extract) was dialyzed against 0.02 M EDTA buffered at pH 7.0 before being applied to the chromatography column. Fractionation of the extract The fractionation was carried out in an 0.8 by 27-cm column of DEAE Sephadex A-50, medium (Pharmacia Fine Chemicals, Sweden), previously equilibrated with 0.02 M EDTA (Kent, 1963). The elution was performed with an NaCl gradient up to 1 M NaCl, obtained by interposing in the line between the reservoir and the column, a 50-ml suction flask containing a magnetic stirring bar. The gradient was started as soon as the extract entered into the resin. The flow rate was 2 to 3 ml/hr and fractions of approximately 1 ml were collected by means of an automatic fraction collector and read with Beckman DU spectrophotometer at 280 m,i. Protein and polysaccharide determination The protein content of the samples was determined by the phenol-biuret reagent of Lowry et al. (1951). The polysaccharide was assayed by the anthrone reagent (Seifter et al., 1950). A glucose standard was always included and the results expressed as glucose.

Treatment of active urinary schistosomiasis in children with sodium antimony dimercapto-succinate by the slow method

BAL present in sodium dimercapto-succinate of antimony does not slow its excretion from the body, but allows for better toleration by the tissues. Still, there are some mild side-reactions that accompany its use in therapy. In Egyptian children it was found that using 50 mg. per kg. body wt., and dividing this total dose into 10 weekly- or twice-weekly injections, 100 per cent. cure rates were obtained. Side-reactions were more numerous in the twice-weekly schedules than the weekly ones. The comparative studies of blood level, urinary excretion and cure rate of the drug to other standard antimonials are given and explained.

Treatment of Schistosomiasis Mansoni with Antimony-a, a′-Dimercapto-Potassium Succinate (TWSb)

IV. Summary and Conclusions TWSb is a water soluble trivalent organic antimonial of a new type, 50 times less toxic than tartar emetic (mouse), applicable by intramuscular and intravenous injection. In laboratory animals TWSb is therapeutically active in Trypanosoma congolense and T. brucei trypanosomiasis, in Litmosoides carinii filariasis and in Manson's schistosomiasis. Seventy clinical cases of active schistosomiasis mansoni have been treated with various intensive intravenous and semi-intensive intramuscular dosage schedules. A one-to-three-day intensive treatment with TWSb has an immediate blocking effect on egg deposition. Immature eggs, numerous before treatment, were conspicuously absent in all of 35 cases submitted to rectal biopsy 2 to 21 days after treatment. In 58 clinical cases of active schistosomiasis mansoni, TWSb permitted a safe 1-to-3-day intensive intravenous treatment with doses totaling 1.1 to 2.3 grams, resulting in 53 (91 per cent) presumptive cures, controlled up to 12 months after the treatment by rectal biopsy and feces examination. Five (9 per cent) of these 58 cases relapsed during the second to sixth post-treatment month. These 5 therapeutic failures received treatment with doses well within the tolerated range, i.e., with doses which can be safely increased. Side effects of the intensive treatment were limited to alimentary vomiting, transitory benign skin rashes and rheumatoid pains toward the end of the treatment. The detoxification of antimony realized in TWSb is particularly evident in electrocardiogram and blood pressure studies demonstrating that even massive doses have no significant cardiovascular effect. The following points suggest TWSb as a medication suited for the public health treatment of schistosomiasis: the rapid treatment within 2 days; the rapid blocking of egg deposition, probably within the first two post-treatment days; the safety of the treatment; the high presumptive cure rate of better than 90 per cent.

Failure of aureomycin in the treatment of schistosomiasis.

Fourteen cases of schistosomiasis were treated with aureomycin at the Santa Ana Clinic, Santurce, Puerto Rico. All patients were from 17 to 43 years of age except for one boy aged 8. All but the boy were discharging Schistosoma mansoni in the feces and the diagnosis was confirmed in 12 instances by rectal biopsy. The 8 year old boy was known to have had active schistosomiasis 2 years before and had been losing weight for several months along with a progressive enlargement of the abdomen. Physical examination revealed markedly enlarged liver and spleen. None of the patients were incapacitated at the time of treatment but 5 were underweight or anemic and one had a mild arteriosclerosis. All reported one or more of the following symptoms: epigastric pain and burning, weakness, dizziness, headache, diarrhea or slight difficulty of vision. Four of the patients had previously been treated with Fuadin and had subsequently relapsed.