Survey on the clinical trial results achieved in Brazil comparing praziquantel and oxamniquine in the treatment of mansoni schistosomiasis

A random, double-blind, parallel group clinical trial program was carried out to compare praziquantel, a recently developed anti-helmintic drug, and oxamniquine, an already established agent for treating mansoni schistosomiasis. Both drugs were administered orally as a single dose, on the average, praziquantel 55 mg/kg and oxamniquine 16 mg/kg BWT. The diagnosis and the parasitological follow-up lasting for a minimum of six months, were based on stool examinations according to Kato/Katz technique. A patient was considered cured if all results were negative and if he had performed at least three post-treatment controls, each one comprising three stool examinations. The finding of a single S. mansoni egg in any stool examination indicated, a therapeutical failure. A total of 267, cases were treated with praziquantel and 272 with oxamniquine. The two groups were homogeneous in regard to patients, age, clinical form of the disease, risk of reinfection and worm burden, relevant factors in the therapeutical response. The incidence and severity of untoward, effects were similar in both groups but abdominal distress and diarrhoea were more frequently reported under praziquantel and dizzines under oxamniquine (p < 0.05). In the former group a marked urticariform reaction was observed whereas in the latter one patient presented convulsion. The laboratory work-up. failed to disclose any significant alteration although the AST, ALT and y-GT mean values revealed a tendence to increase on the 7th day after oxamniquine intake. The overall parasitological cure rates were 75.5% (139/ 184) with praziquantel and 69.8% (134/192) with oxamniquine (p > 0.05). Amongst the noncured aptients a reduction of 88.6% and 74.6% in the mean number of eggs/g of feces Was seen following the treatment with praziquantel and oxamniquine, respectively (p < 0.05). In conclusion, in spite of their different chemical, pharmacological and toxicological profiles as well as mechanisms-of-action, inclusively praziquantel already had proved to be 100% active against S. mansoni strains resistant to oxamniquine, both drugs showed comparable tolerance and therapeutical efficacy.

Chronic myocardial damage in experimental T. cruzi infection of a new world primate, Cebus sp. monkey

Eighteen Cebus apella monkeys, (juvenile and adult of both sexes) were inoculated five years ago, with three Trypanosoma cruzi strains (CA1, n = 10; Colombian, n=4 and Tulahuen, n=4), either by conjunctival or intraperitoneal route, once or repeatedly. Parasitological, hematological, serological, enzymatic, radiographic, electro and echocardiographic findings have been peviously published15 and they are similar to those observed in human pathology. The most frequent electrocardiographic alteration was right branch bundle block. Six animals, chosen at random, were sacrificed. Those sacrificed 20 to 25 months post-first inoculation showed focal accumuli of leukocytes with myocytolysis. Foci of diffuse interstitial fibrosis with mild infiltrate of leukocytes among fibers were observed in the animals sacrificed 36 to 47 months post-inoculation. No parasites were seen. The lesions were more prominent in the ventricular walls and the septum. The fact that the infiltrates were predominant in the animals sacrificed at a shorter time after first inoculation and that fibrosis was more severe in those sacrificed at a longer time suggests that there is a progression of the infiltrative lesions to fibrosis, with a leukocytic activity indicative of a chronic phase. These lesions are similar to those described in human chronic Chagas' disease. This would demonstrate that this model is useful in evaluating a progress in the knowledge of the pathogenesis which is still a controversial issue, immunology, immunogenesis and chemotherapeutic agents of the chronic and indeterminate phases of this disease.

Pentavalent antimonial nephrotoxicity in the rat

Aspects of the renal function were assessed in rats treated with the pentavalent antimonials Glucantime (Meglumine Antimoniate, Rhodia) or Pentostam (Sodium Stibogluconate, Wellcome). In dose of 30 mg of Sb v (Glucantime or Pentostam) by 100 mg of weight by day for 30 days, renal functional changes were observed consisting of disturbances in urine concentrating capacity. Such disturbances were expressed by significantly low values of urine osmolality as compared to the basal values previous to the drugs. The decrease in urine osmolality was associated to a significant increase in urinary flow and in negative free-water clearance. There was no alteration in osmolar clearance and in fractional excretion of sodium. These observations suggest an interference of the drugs in the action of the antidiuretic hormone. The disturbance in urine concentration was reversible after a seven days period without the drugs administration. No significant histopathological alterations were observed in the kidneys of the rats treated with the drugs. On the other hand, the rats treated with a high dose of Pentostam (200 mg/100 grams of weight/day) showed the functional and the histopathological alterations of the acute tubular necrosis.

Clinical and endoscopic findings in the mucosae of the upper respiratory and digestive tracts in post-treatment follow-up of paracoccidioidomycosis patients

Systematic examination of the upper respiratory and digestive tracts (URDT) was performed in a group of 80 paracoccidioidomycosis (PCM) patients submitted to post-treatment follow-up ranging from 8 months to 17 years. Mucosae of the URDT had been involved prior to specific treatment in 74 patients, distributed as follows: oropharynx, 50 (41 alone, 7 in association with the larynx, and 2 with the nasal mucosa); larynx, 30 (23 alone and 7 in association); and nasal mucosa, 3(1 alone and 2 in association). Inactive lesions were observed in all the 50 patients with lesions of the oropharynx, 3 of whom with deforming scars (1 with retraction of the tongue and 2 with narrowing of the oral orifice). One case presented a destructive lesion, with perfuration of the palate. Of the other 46 cases, examination showed nacreous white striated scars which were nearly imperceptible in some cases and in others displayed partial retraction of anatomical structures without any alteration of their features. Patients presented a high rate of missing teeth. In 3 patients with involvement of the nasal mucosa, none of whom presented active PCM lesions, 2 still had nasal voices. In 30 patients with lesions of the larynx, 1 suffered a relapse of PCM and 2 developed epidermoid carcinoma. Of the other 27 cases, none of whom had active PCM lesions, 15 presented dysphonia, 3 were tracheotomized, and 9 were asymptomatic.

The value of adenosine deaminase (ADA) determination in the diagnosis of tuberculous ascites

In order to evaluate the role of the determination of adenosine deaminase activity (ADA) in ascitic fluid for the diagnosis of tuberculosis, 44 patients were studied. Based on biochemical, cytological, histopathological and microbiological tests, the patients were divided into 5 groups: G1 - tuberculous ascites (n = 8); G2 - malignant ascites (n = 13); G3 - spontaneous bacterial peritonitis (n = 6); G4 - pancreatic ascites (n = 2); G5 - miscelaneous ascites (n = 15). ADA concentration were significantly higher in G1 (133.50 ± 24.74 U/l) compared to the other groups (G2 = 41.85 ± 52.07 U/l; G3 = 10.63 ± 5.87 U/l; G4 = 18.00 ± 7.07 U/l; G5 = 11.23 ± 7.66 U/l). At a cut-off value of >31 U/l, the sensitivity, specificity and positive and negative preditive values were 100%, 92%, 72% and 100%, respectively. ADA concentrations as high as in tuberculous ascites were only found in two malignant ascites caused by lymphoma. We conclude that ADA determination in ascitic fluid is a useful and reliable screening test for diagnosing tuberculous ascites. Values of ADA higher than 31 U/l indicate more invasive methods to confirm the diagnosis of tuberculosis.

Effect of b-Propiolactone treatment on the complement activation mediated by equine antisera

Reduction of complement activation through an alteration of the Fc fragment of immunoglobulins by b-propiolactone treatment was carried out in equine antisera raised against rabies virus, Bothrops venoms and diphtherial toxin. Results were evaluated by means of an anaphylactic test performed on guinea-pigs, and compared to the ones obtained with the same sera purified by saline precipitation (ammonium sulfate), followed or not by enzymatic digestion with pepsin. Protein purity levels for antibothropic serum were 184.5 mg/g and 488.5 mg/g in b-propiolactone treated and pepsin-digested sera, respectively. The recovery of specific activity was 100% and 62.5% when using antibothropic serum treated by b-propiolactone and pepsin digestion, respectively. The antidiphtherial and anti-rabies sera treated with b-propiolactone and pepsin presented protein purity levels of 5,698 and 7,179 Lf/g, 16,233 and 6,784 IU/g, respectively. The recovery of specific activity for these antisera were 88.8%, 77.7%, 100% and 36,5%, respectively. b-propiolactone treatment induced a reduction in complement activation, tested "in vivo", without significant loss of biological activity. This treatment can be used in the preparation of heterologous immunoglobulins for human use.

QUANTIFICATION OF THE POPULATION AND PHAGOCYTARY ACTIVITY OF HEMOCYTES OF RESISTANT AND SUSCEPTIBLE STRAINS OF Biomphalaria glabrata AND Biomphalaria tenagophila INFECTED WITH Schistosoma mansoni

Among the determinant factors in the resistance and susceptibility of Biomphalaria to Schistosoma mansoni, hemocytes play an important role. Aiming at studying S. mansoni/Biomphalaria interactions related to hemocytes, the first step is certainly connected with the standardization of this cell population in uninfected Biomphalaria. In this way, quantification of this cell population in hemolymph, as well as its phagocitary capacity, have been determined for the first time. Furthermore, using susceptible and resistant strains of B. glabrata and B. tenagophila, the hemocytegram and phagocytary capacity of hemocytes after infection with S. mansoni were determined too. Resistant and susceptible strains of B.glabrata (BA and BH, respectively), as well as resistant and susceptible strains of B. tenagophila (Taim and CF, respectively) were infected with 10 miracidia of the LE and SJ strains of S. mansoni, respectively. These infected snails and respective uninfected controls were assessed in relation to the number of circulating hemocytes and alteration in the phagocytary capacity, by using Zymozan and MTT. Reading was taken by means of a spectrophotometer at 5 hours and 1,2,5,10,20 and 30 days after infection. The results showed a decrease in population of the circulating phagocytary cells, 5 hours after infection. One day post-infection, the circulating cells of the susceptible snails showed an increased metabolic activity, but the same event could not be observed in the resistant strains. In the subsequent observation periods, significant differences among the strains studied could not be observed until the end of the experiment

EXPERIENCE IN THE EVALUATION OF CHILDREN WITH HEPATOSPLENOMEGALY AT A TEACHING AMBULATORY, SÃO PAULO, BRAZIL

Objectives: Describe cases of children with hepatosplenomegaly (HS) attended at the General Pediatric Teaching Ambulatory (AGER) of Instituto da Criança, São Paulo, identifying the main causes, evolution, necessity for hospitalization and/or referral to specialists. Methodology: Retrospective analysis of the records of children presenting HS on admission at AGER from September 1, 1993 to August 31, 1996. Results: Of the 89 children included (age range, 1 to 148 months; median, 24 months), 64 (72%) were referred from other services for HS investigation. Most common presenting complaints were: fever - 39 (44%); pallor - 26 (29%); weight loss - 21 (24%) and jaundice - 14 (16%). Main alterations noticed on physical examination were: pallor - 47 (53%) and short stature - 17 (19%). Anemia was diagnosed in 70 children (79%); 35 children (39%) had infections; 7 (8%) metabolic disorders and 5 (6%) neoplastic disorders. The most frequent infections were of the urinary tract - 9 (10%) and hepatitis A - 6 (7%).Thirty six children (40%) were referred to specialists, 17 of which were already diagnosed. Conclusions: Most of the children with HS present deficiency anemia associated with infections which the general pediatrician is able to diagnose. Persistence of unexplained HS for more than 2 months, especially when there is substantial volume enlargement or alteration in the organs consistency, is an indication for referral to specialists.

The effect of antioxidant properties of aqueous garlic extract and Nigella sativa as anti-schistosomiasis agents in mice

The aim of this study was to assess the antioxidant and anti-schistosomal activities of the garlic extract (AGE) and Nigella sativa oil (NSO) on normal and Schistosoma mansoni-infected mice. AGE (125 mg kg-1, i.p.) and NSO (0.2 mg kg-1, i.p.) were administrated separately or in combination for successive 28 days, starting from the 1st day post infection (pi). All mice were sacrificed at weeks 7 pi. Hematological and biochemical parameters including liver and kidney functions were measured to assess the progress of anemia, and the possibility of the tissue damage. Serum total protein level, albumin, globulin and cholesterol were also determined. Malondialdehyde (MDA) and glutathione (GSH) levels were determined in the liver tissues as biomarkers for oxidative and reducing status, respectively. The possible effect of the treatment regimens on Schistosoma worms was evaluated by recording percentage of the recovered worms, tissue egg and oogram pattern. Result showed that, protection with AGE and NSO prevented most of the hematological and biochemical changes and markedly improved the antioxidant capacity of schistosomiasis mice compared to the infected-untreated ones. In addition, remarkable reduction in worms, tissue eggs and alteration in oogram pattern were recorded in all the treated groups. The antioxidant and antischistosomal action of AGE and NSO was greatly diverse according to treatment regimens. These data point to these compounds as promising agents to complement schistosomiasis specific treatment.

Impact of Taraxerol in combination with extract of Euphorbia tirucalli plant on biological parameters of Lymnaea acuminata

The present work was carried out to evaluate the molluscicidal activity of active ingredient Taraxerol with the acetone extract of Euphorbia tirucalli against Lymnaea acuminata snail. The (fecundity, hatchability and survivability) of snail L. acuminata exposed to this extract was studied. The effects of the tested extracts on life-history traits of harmful snail L. acuminata have also been evaluated, and this study also expounds the inhibitory effects of these extracts singly as well as in binary combination (1:1 ratio). It concluded that these herbal products act as a potential source of molluscicides, and that they would also have the advantage of easy availability, low cost, biodegradability and greater acceptance amongst users than synthetic pesticide.

Prevalence of intestinal nematodes in alcoholic patients

We report the results of a retrospective study on the frequency of intestinal nematodes among 198 alcoholic and 440 nonalcoholic patients at the University Hospital Cassiano Antonio Moraes in Vitória, ES, Brazil. The control sample included 194 nonalcoholic patients matched according to age, sex and neighborhood and a random sample of 296 adults admitted at the same hospital. Stool examination by sedimentation method (three samples) was performed in all patients. There was a significantly higher frequency of intestinal nematodes in alcoholics than in controls (35.3% and 19.2%, respectively), due to a higher frequency of Strongyloides stercoralis (21.7% and 4.1%, respectively). Disregarding this parasite, the frequency of the other nematodes was similar in both groups. The higher frequency of S. stercoralis infection in alcoholics could be explained by immune modulation and/or by some alteration in corticosteroid metabolism induced by chronic ethanol ingestion. Corticosteroid metabolites would mimic the worm ecdisteroids, that would in turn increase the fecundity of females in duodenum and survival of larvae. Consequently, the higher frequency of Strongyloides larvae in stool of alcoholics does not necessarily reflect an increased frequency of infection rate, but only an increased chance to present a positive stool examination using sedimentation methods.

Dynamics and kinetics of natural killer cell cytotoxicity in human malaria as evaluated by a novel stepwise cytotoxicity assay

Malaria causes important functional alterations of the immune system, but several of them are poorly defined. To evaluate thoroughly the natural killer cell cytotoxicity in patients with malaria, we developed a technique capable to assess both the dynamics and the kinetics of the process. For the kinetics assay, human peripheral blood mononuclear cells were previously incubated with K562 cells and kept in agarose medium, while for the dynamics assay both cells were maintained in suspension. NK activity from patients with vivax malaria presented a kinetics profile faster than those with falciparum malaria. NK cytotoxicity positively correlated with parasitemia in falciparum malaria. The dynamics of NK cytotoxicity of healthy individuals was elevated at the beginning of the process and then significantly decreased. In contrast, malaria patients presented successive peaks of NK activity. Our results confirmed the occurrence of alteration in NK cell function during malaria, and added new data about the NK cytotoxicity process.

Gallbladder neuron count in cholelithiasis patients with and without Chagas disease

Various investigators agree that the incidence of cholelithiasis is greater in patients with Chagas disease. The most plausible explanation for this is based on the parasympathetic denervation that occurs over the whole digestive tract due to Chagas disease. In order to analyze the occurrence of this alteration, gallbladder neuron counts were performed on cholelithiasis patients with and without Chagas disease who were being treated at the Department of Digestive Surgery, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil. In the present study, a notable reduction in the number of neurons in the gallbladder wall was observed in Chagas patients, in comparison with non-Chagas subjects.

Scorpionism due to Tityus neoespartanus (Scorpiones, Buthidae) in Margarita Island, northeastern Venezuela

The first two cases of scorpion envenoming caused by Tityus neoespartanus (Buthidae) are described. The accidents took place within human environments (one inside a home and the other inside a school), in the village of La Sierra, Margarita Island, State of Nueva Esparta, northeastern Venezuela. Both cases were moderately severe and developed pancreatic involvement and electrocardiographic abnormalities. This report allows inclusion of Margarita Island among the endemic areas of scorpionism in Venezuela.

Aedes aegypti and Aedes albopictus (Diptera: Culicidae): coexistence and susceptibility to temephos, in municipalities with occurrence of dengue and differentiated characteristics of urbanization

INTRODUCTION: The aim of the present study was to verify the coexistence between Aedes aegypti and Aedes albopictus populations in municipalities of the States of Paraná and Santa Catarina with different urbanization profiles where dengue occurs and evaluate their susceptibility to the organophosphate temephos. METHODS: The number of eggs per ovitrap were counted and incubated for hatching to identify the species. Data analysis of the populations was conducted to determine randomness and aggregation, using the variance-to-mean ratio (index of dispersion). Susceptibility to temephos was evaluated by estimation of the resistance ratios RR50 and RR95. Aedes aegypti samples were compared with the population Rockefeller and Aedes albopictus samples were compared with a population from the State of Santa Catarina and with the Rockefeller population. RESULTS: Coexistence between Aedes aegypti and Aedes albopictus and the aggregation of their eggs were observed at all the sites analyzed in the State of Paraná. CONCLUSIONS: All the Aedes aegypti populations from the State of Parana showed alteration in susceptibility status to the organophosphate temephos, revealing incipient resistance. Similarly, all the Aedes albopictus populations (States of Paraná and Santa Catarina) presented survival when exposed to the organophosphate temephos.