Chronic glomerulonephritis associated with hepatosplenic schistosomiasis mansoni

In a series of 36 cases of renal disease associated with hepatosplenic schistosomiasis the following morphologic types of glomerulonephritis were found: mesangio-capillary (33.2%), mesangial proliferative (25.0%), focal glomerular sclerosis (16.7%) and sclerosing glomerulonephritis (8.3%). No significant statistical differences were found when these results were compared with those from 36 cases of glomerulonephritis not associated with hepatosplenic disease. On the other hand, endocapillary glomerulonephritis was found to be predominant in the latter group of cases. These results did not substantiate the assumption that mesangio-capillary glomerulonephritis is specifically related to hepatosplenic schistosomiais. However, if the types of glomerulonephritis that predominantly involve the me-sangium are considered together, they are significantly associated with hepatosplenic schistosomiasis. Mesangial involvement is known to occur in other parasitic diseases and that may be related to a common immunopathogenesis.

Therapeutical evaluation of different dose regimens of praziquantel in schistosomiasis mansoni, based on the quantitative oogram technique

A clinical trial involving 80 patients of both sexes, from ages 15 to 55, with chronic intestinal or hepatointestinal schistosomiasis mansoni, was carried out to evaluate the therapeutical efficacy of different dose regimens of praziquantel. The patients were randomly allocated into four groups with an equal number of cases and were then treated with one of the following dosages: 60 mg/kg for 1 day; 60 mg/kg daily for 2 days; 60 mg/kg daily for 3 days; and 30 mg/kg daily for 6 days. The assessment of parasitological cure was based on the quantitative oogram technique through rectal mucosa biopsies which were undertaken prior to, as well as, 1,2,4 and 6 months post-treatment. Concurrently, stool examinations according to the qualitative Hoffman, Pons & Janer (HPJ) and the quantitative Kato-Katz (K-K) methods were also performed. The best tolerability was observed with 30 mg/kg daily for 6 days whereas the highest incidence of side-effects (mainly dizziness and nausea) was found with 60 mg/kg daily for 3 days. No serious adverse drug reaction has occurred. The achieved cure rates were: 25% with 60 mg/kg for 1 day; 60% with 60 mg/kg daily for 2 days; 89.5% with 60 mg/kg daily for 3 days; and 90% with 30 mg/kg daily for 6 days. At the same time there has been a downfall of 64%, 73%, 87% and 84% respectively, in the median number of viable S. mansoni ova per gram of tissue. Thus, a very clear direct correlation between dose and effect could be seen. The corresponding cure rates according to stool examinations by HPJ were 39%, 80%, 100% and 95%; by K-K 89%, 100%, 100% and 100%. This discrepancy in results amongst the three parasitological methods is certainly due to their unequal accuracy. In fact, when the number of viable eggs per gram of tissue fell below 5,000 the difference in the percentage of false negative findings between HPJ (28%) and K-K (80%) became significative. When this number dropped to less than 2,000 the percentage of false negative results obtained with HPJ (49%) turned significant in relation to the oogram as well. In conclusion, it has been proven that praziquantel is a highly efficacious agent against S. mansoni infections. If administered at a total dose of 180 mg/kg divided into either 3 or 6 days, it yields a 90% cure rate. Possibly, one could reach 100% by increasing the total dose to 240 mg/kg. Furthermore, it was confirmed that the quantitative oogram technique is the most reliable parasitological method when evaluating the efficacy of new drugs in schistosomiasis mansoni.

Efficacy of oxamniquine, praziquantel and a combination of both drugs in schistosomiasis mansoni in Brazil

A randomized clinical trial was carried out to compare the efficacy of a low-dosage combination of oxamniquine (7.5 mg/kg) plus praziquantel (20 mg/kg) against either agent, oxamniquine (15 mg/kg) or praziquantel (40 mg/kg) alone, in the treatment of schistosomiasis mansoni in the Brazilian north-east. The drugs were randomly administered per os to 91 patients. Six and twelve months after treatment 89% of those admitted to the trial were reexamined by Kato-Katz method (ten slides) and MIF technique (one gram of stool) The achieved cure rates, as defined by absence of S. mansoni eggs in the faeces of individual patients at all points during the parasitological follow-up, were 81.8%, 81.2% and 67.6% for praziquantel, oxamniquine and the combination respectively. The reduction of eggs excretion in non cured patients six months after therapy ranged from 93.8-96.8% with praziquantel, 32.5-97% with oxamniquine and 76.9-99.5% with the combination. It is concluded that, at the used dosages, the three therapeutical regimens give similar and satisfactory results in the treatment of uncomplicated S. mansoni infection in Brazil.

Hypoprothrombinemia in the compensated form of hepatosplenic schistosomiasis: further studies

Coagulation abnormality is frequently observed in schistosomiasis patients but its pathophysiology has not been established. We measured, by immunodiffusion. the prothrombin-antigen concentration in 56 individuals; of these 19 with demonstrated compensated form of hepatosplenic schistosomiasis, 17 with cirrhosis and 20 were control subjects. Transaminases, albumin, transthyretin, prothrombin time, antithrombin III, factor VII, and fibrinogen were also evaluated. All parameters were altered in the cirrhotic group but only albumin, prothrombin and antithrombin III levels were altered in the schistosomiasis group. Ninety percent of the patients with cirrhosis and sixty percent of the patients with schistosomiasis had abnormal plasma levels of albumin, transthyretin, prothrombin-antigen, and/or antithrombin III; an impaired hepatic synthesis was responsible for these results. Conversely forty percent of the schistosomiasis patients with normal plasma concentrations of both albumin and transthyretin had decreased mean plasma levels of both prothrombin and antithrombin III. These results suggest that either proth rombin and antithrombin III are more sensitive markers of impaired hepatic synthesis in schistosomiasis than are levels of albumin and transthyretin combined, or a low grade chronic consumption of clotting proteins also occurs. Considering the latter hypothesis it is possible that the thrombin formed would be inhibited by antithrombin III with the complexed thrombin-antithrombin III being cleared by the liver. Consequently the plasma levels of both prothrombin and antithrombin would be decreased, but the level of fibrinogen would be preserved.

Immunopathology of human schistosomiasis mansoni: I. Immunomodulatory influences on T cell function

Cell mediated immune response was studied in patients with recent and chronic Schistosoma mansoni infection. Precultured peripheral mononuclear cells showed significantly higher responses to S. mansoni adult worm antigen (SAWA) when compared to fresh cell preparations. The addition of each patient serum to the precultured cells reactions to SAWA or recall antigens demonstrated a strong inhibitory serum action, which was also noted on allogeneic cells derived from healthy subjects. The CD4 subset was the main responding cell to SAWA being this reactivity highly suppressed by the presence of the monocyte macrophage accessory cells. We stressed the simultaneous inhibitory action of humoral and cellular factors on the specific cell response to S. mansoni.

Immunopathology of human schistosomiasis mansoni: II. NK activity and stimulation by specific antigen

Sixteen S. mansoni infected and untreated patients (5 with recent infection and 11 with chronic disease) were evaluated for their in vitro natural killer (NK) activity against the NK sensitive target K562 cell line. NK levels in 9 out of 11 patients (82%) with chronic disease were significantly lower (mean = 15 ± 6%),compared with patients recently infected (mean = 41 ± 9% p < 0.001) and with the control group (mean = 38 ± 13% p < 0.001). However, both patients and controls NK activity was stimulated by soluble adult worm antigens (SAWA), indicating that NK function even in the chronic stage of the infection is able to respond to the parasite antigens. These results suggest the possibility of NK cell participation as effector mechanism against S. mansoni.

Schistosomiasis mansoni in the municipality of Pedro de Toledo (São Paulo, Brazil) where the Biomphalaria tenagophila is the snail host: I - Prevalence in human population (

Due to the scarce information about the epidemiological features of schistosomiasis in which the vector is Biomphalaria tenagophila, an investigation was carried in Pedro de Toledo in 1980 where such peculiarity is observed. Stool examinations (Kato-Katz method) were performed in 4,741 individuals (22.8% positive to Schistosoma mansoni eggs) of this 583 had previously received chemoterapy and 4,158 remainders, untreated. The schistosomiasis prevalence in those two groups where respectively 31.7% and 21.6%. Epidemiological investigation showed that 83.6% were autochthonous cases from the studied area: the autochthonous prevalence rate, and the intensity of infection in the untreated autochthonous cases were higher in males than in females; the intensity in the latter untreated group was low, 58.5 eggs/g feces (geometric mean). Moreover, according to the age groups the intensity of infections correlated well (r s = 0.745) with the prevalence rates. Schistosomiasis was verified to occur mostly during the leisure time and by the use of water streams for housework in rural zone. Only 0.4% out of 1,137 snails was positive for S. mansoni cercariae, apparently unchanged from the 1978 study when the human prevalence was 12.0%. The studied area presented differences and similarities in relation to the other Brazilian areas were the main intermediate host is B. glabrata.

Reinfection after treatment of schistosomiasis: environment or "predisposition"?

Although very efficient for the control of morbidity due to S. mansoni in individual patients, chemotherapy has not proven successful in the management of transmission within hyperendemic areas when used alone, even if repeated at short intervals. Consequently, a great deal of effort has been expended toward immunologic investigation and development of a specific vaccine. Based upon a study of a group of children (5-14 years) from the state of Alagoas, the author demonstrates that the outcome one year after chemotherapy depends essentially on the "risk rating" of the area of domicile. A regression analysis did not reveal significant correlation to neither age, sex or initial egg counts. Although the study was not designed to reveal individual variations in the immune status, it is postulated that putative differences in genetic make-up are irrelevant in terms of large-scale intervention. Since morbidity due to S. mansoni has substantially declined during the last two or three decades, a control policy based on vaccination can only be justified if high levels of protective immunity can be attained. At any rate, such a vaccine will have to be administered in early childhood (preferably below the age of three). It can also be demonstrated that immunization in adolescence or adulthood serves no purpose whatsoever. The author is convinced that environmental intervention, usually dismissed as unrealistic in terms of the developing countries, is not only feasible, if done on a selective basis, but prioritary.

Schistosomiasis mansoni in an area of low transmission: I. impact of control measures

This work was undertaken in the municipality of Pedro de Toledo (São Paulo State, Brazil) in 1987, to clarify aspects related to the transmission levels of Schistosoma mansoni in a human population where the snail host is Biomphalaria tenagophila. Since 1980 a control programme has been undertaken in this municipality. Urban and rural populations (4,719 subjects) were submitted to faecal examinations (Kato-Katz method). The overall prevalence rate was 4.8% being higher in males (6.2%) and also in the rural zone (5.8%). The geometric mean of S. mansoni eggs was 35.1 eggs per gramme of faeces (epg). Approximately 80.0% of the carriers presented less than 100 epg and only 20 individuals (9.0%) eliminated more than half of total eggs. The highest index of potencial contamination (IPC) was in the age group of 5 to 20 years (57.6%). Two thirds of the investigated patients (207) were autochthonous of Pedro de Toledo. The geographical distribution of the carriers showed a clear aggregation of the autochthonous cases and a close association between human contact sites and breeding places of B. tenagophila. This study shows that schistosomiasis subjects were not randomly aggregated, the youngsters should be the main target in the prophylaxis, and the efficacy of the control programme.

Pathology of periportal fibrosis involution in human schistosomiasis

Optical and electron microscopical evidences of focal matrix degradation were frequently seen in liver sections of periportal fibrosis caused by schistosomiasis mansoni in man. The material came from 14 wedge hepatic biopsies taken from patients with chronic advanced hepatosplenic disease and undergoing operations for the relief of portal hypertension. Besides the presence of focal areas of rarefaction, fragmentation and dispersion of collagen fibers, the enlarged portal spaces also showed hyperplasia of elastic tissue and disarray of smooth muscle fibers following destruction of portal vein branches. Eggs were scanty in the tissue sections, and matrix degradation probably represented involuting changes related to the progressive diminution of parasite-related aggression, which occurs spontaneously with age or after cure by chemotherapy. The changes indicative of matrix degradation now described are probably the basic morphological counterpart of periportal fibrosis involution currently being documented by ultrasonography in hepatosplenic patients submitted to curative chemotherapy.

Optimization of HS-SPME analytical conditions using factorial design for trihalomethanes determination in swimming pool water samples

Trihalomethanes (THMs) are widely referred and studied as disinfection by-products (DBPs). The THMs that are most commonly detected are chloroform (TCM), bromodichloromethane (BDCM), chlorodibromomethane (CDBM), and bromoform (TBM). Several studies regarding the determination of THMs in swimming pool water and air samples have been published. This paper reviews the most recent work in this field, with a special focus on water and air sampling, sample preparation and analytical determination methods. An experimental study has been developed in order to optimize the headspace solid-phasemicroextraction (HS-SPME) conditions of TCM, BDCM, CDBM and TBM from water samples using a 23 factorial design. An extraction temperature of 45 °C, for 25min, and a desorption time of 5 min were found to be the best conditions. Analysis was performed by gas chromatography with an electron capture detector (GC-ECD). The method was successfully applied to a set of 27 swimming pool water samples collected in the Oporto area (Portugal). TCM was the only THM detected with levels between 4.5 and 406.5 μg L−1. Four of the samples exceeded the guideline value for total THMs in swimming pool water (100 μgL−1) indicated by the Portuguese Health Authority.

Nephrotic syndrome associated with hepatointestinal schistosomiasis

Schistosomal nephropathy has long been related to the hepatosplenic form of schistosomiasis. In the last few years, 24 patients with hepatointestinal schistosomiasis and the nephrotic syndrome were studied. Aiming at evaluating a possible etiologic participation of schistosomiasis in the development of the nephropathy, this group was comparatively studied with a group of 37 patients with idiopathic nephrotic syndrome. Both groups had a different distribution of the histologic lesions. In the group with schistosomiasis there was a statistically significant prevalence of proliferative mesangial glomerulonephritis (33.3%), whereas in the control group there was prevalence of membranous glomerulonephritis (32.4%). On immunofluorescence, IgM was positive in 94.4% of the patients with schistosomiasis versus 55.0% in the control group (p<0.01). In the group with schistosomiasis, 8 patients evidenced mesangial proliferative glomerulonephritis and 5, membra-noproliferative glomerulonephritis. In both histological types immunofluorescence showed IgM and C3 granular deposits in the glomeruli. The data in this study suggests that mesangial proliferative and membranoproliferative glomerulonephritis, with glomerular granular IgM and C3 deposits, represent the renal lesions of the schistosomiasis associated nephropathy.

A municipal level approach to the management of schistosomiasis control in Peri-Peri, MG, Brazil

A schistosomiasis control program was implemented between 1974/87 in Peri-Peri,. MG (622 inhabitants). Molluscicide (niclosamide) was applied at three monthly intervals in water sources with Biomphalaria glabrata, and individuals eliminating Schistosoma mansoni eggs in the feces were treated annually with oxamniquine. From 1974 to 1983 the control measures were undertaken by staff of the "René Rachou" Research Center FIOCRUZ (CPqRR), and from 1984 to 1987 these measures were included in the Capim Branco basic health network activities. During both periods, the prevalence, incidence, intensity of infection and hepatosplenic form as well as the number of infected snails decreased significantly. The prevalence decreased from 43.5 to 4.4%, the incidence from 19.0 to 2.9%, the overall intensity of S. mansoni from 281 to 87 and of the hepatosplenic form from 5.9 to 0.0%. The results obtained suggest that the municipal management of control measures was as effective as the vertical program conducted by CPqRR staff.

Stool examination and rectal biopsy in the diagnosis and evaluation of therapy of schistosomiasis mansoni

From each of a group of 217 adult males selected through enzyme-immunoassay or skin-test (Group A), six stool samples were examined by both the Lutz/Hoffman, Pons & Janer (Lutz/HPJ) and Kato/Katz methods. In addition, one oogram of the rectal mucosa was performed. By these methods, schistosomiasis was detected in 44.7%, 47.5% and 40.1% of the individuals respectively. To evaluate the methods in the assessment of cure, the last 40 patients from group A, treated with a single oral dose of oxamniquine at 15 mg/kg were followed up for six months (Group B). The criteria for parasitological cure included three stool examinations by Kato/Katz and Lutz/HPJ methods, one, three and six months post-treatment and a rectal biopsy between the fourth and sixth months post-treatment. The examinations were negative in 87.5%, 90% and 95% of the patients, respectively. The efficacy of oxamniquine was 82.5% when the three methods were considered together and there was no statistically significant difference between the sensitivity of the individual methods.