Luiz Candido de Souza Dias

Use of praziquantel in patients with schistosomiasis mansoni previously treated with oxamniquine and/ or hycanthone: resistance of Schistosoma mansoni to schistosomicidal agents.

Fourteen patients with active schistosomiasis mansoni in spite of previous treatment with oxamniquine and/or hycanthone were treated with praziquantel, single oral dose of 45 to 50 mg/kg body-weight. All underwent clinical, laboratory and electrocardiographic examination before and after treatment. Untoward effects (dizziness, drowziness, nausea and abdominal pain) were observed in ten. Laboratory findings disclosed no significant alteration and the electrocardiograms showed no abnormalities. Monthly follow-up examinations of 13 patients for six consecutive months showed parasitological cure in all. Before praziquantel treatment strains of Schistosoma mansoni were isolated from two patients, one treated three times with oxamniquine and the other with hycanthone once and oxamniquine twice. Progenies of these strains were maintained in Biomphalaria glabrata and mice. Groups of these infected mice were then treated with oxamniquine, hycanthone, niridazole and praziquantel and results compared with the BH strain maintained in our laboratory for many years. Schistosomicidal activity was assessed by the localization of worms in the portal vein system and oogram changes. Progenies from the strains isolated in this study were resistant to oxamniquine and hycanthone but sensitive to niridazole and praziquantel. The BH strain was sensitive to all four drugs. The serial runs of S. mansoni strains through intermediate and definitive hosts have not influenced their reactions to these schistosomicides.

Response of drug resistant isolates of Schistosoma mansoni to antischistosomal agents

The susceptibility of four isolates of Schistosoma mansoni (BH, MAP, MPR-1 and K) to four multiple doses of anti-schistosomal agents (hycanthone, niridazole, oxamniquine, and praziquantel) were evaluated in infected female Swiss albino mice. These schistosomal isolates had been maintained in the laboratory without further drug pressure for 20 to 30 generations. Multiple dosage regimens were used for each drug against each isolate of S. mansoni to generate ED50 (effective dose 50%) values. Results demonstrated that the K isolate is resistant to niridazole, the MPR-1 isolate to oxamniquine, and the MAP isolate to both hycanthone and oxamniquine. The BH isolate was susceptible to all drugs and was used as the reference isolate. All isolates were susceptible to parziquantel. The significance of the difference in response of the MPR-1 and MAP isolates is discussed. These results confirm the resistance of these isolates of S. mansoni to three schistosomicides and demonstrate that the resistance of these isolates are stable over long periods of time without exposure to drugs.

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 potential 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.

Drug resistance in Schistosomiasis: a review

Drug resistance associated with the treatment of human schistosomiasis appears to be an emerging problem requiring more attention from the scientific community than the subject currently receives. Drug-resistant strains of Schistosoma mansoni have been isolated by various investigators as a result of laboratory experimentation or from a combination of field and laboratory studies. Review of this data appears to indicate that the lack of susceptibility observed for some of the isolated strains cannot be ascribed solely to previous administration of antischistosome drugs and thus further studies are required to elucidate this phenomena. Strains of S. mansoni have now been identified from Brazil which are resistant to oxamniquine, hycanthone and niridazole; from Puerto Rico which are resistant to hycanthone and oxamniquine; and from Kenya which are resistant to niridazole and probably oxamniquine. Strains derived by in vitro selection and resistant to oxamniquine and possibly to oltipraz are also available. All of these strains are currently maintained in the laboratory in snails and mice, thus providing for the first time an opportunity for indepth comparative studies. Preliminary data indicates that S. haematobium strains resistant to metrifonate may be occurring in Kenya. This problem could poise great difficulty in the eventual development of antischistosomal agents. Biomphalaria glabrata from Puerto Rico and Brazil were found to be susceptible to drug-resistant S. mansoni from each country.

DETECTION OF IgM ANTIBODIES TO Schistosoma mansoni GUT-ASSOCIATED ANTIGENS FOR THE STUDY OF THE DYNAMICS OF SCHISTOSOMIASIS TRANSMISSION IN AN ENDEMIC AREA WITH LOW WORM BURDEN

For a period of 2 years, five follow-up measures of prevalence and incidence rates were estimated in a prospective study of S. mansoni infection in a group of schoolchildren who were living in a rural area of the Municipality of Itariri (São Paulo, Brazil), where schistosomiasis is transmitted by Biomphalaria tenagophila. Infection was determined by the examination of three Kato-Katz stool slides, and the parasitological findings were analyzed in comparison to serological data. In the five surveys, carried out at 6-month intervals (March-April and September-October), the prevalences were, respectively, 8.6, 6.8, 9.9, 5.8 and 17.2% by the Kato-Katz, and 56.5, 52.6, 60.8, 53.5 and 70.1% by the immunofluorescence test (IFT). Geometric mean egg counts were low: 57.8, 33.0, 35.6, 47.3 and 40.9 eggs per gram of feces, respectively. Of the total of 299 schoolchildren, who submitted five blood samples at 6-month intervals, one for each survey, 40% were IFT-positive throughout the study, and 22% were IFT-negative in all five surveys. Seroconversion from IFT negative to positive, indicating newly acquired S. mansoni infection, was observed more frequently in surveys carried out during March-April (after Summer holidays), than during September-October. Seasonal trends were not statistically significant for detection of S. mansoni eggs in stool. The results indicate that the use of IgM-IFT is superior to parasitological methods for detection of incidence of S. mansoni infection in areas with low worm burden.

Schistosomiasis mansoni in an area of low transmission: II. Risk factors for infection

Risk factors for Schistosoma mansoni infection were identified using a 1:1 matched case-control design. The work was conducted in the municipality of Pedro de Toledo, São Paulo State, Brazil, an area where the snail host is Biomphalaria tenagophila. Information on water contact patterns, knowledge, attitudes and practices (kap), socioeconomic and sanitary conditions were obtained by mean of questionnaires. The crude odds ratio estimates and the adjusted odds ratio estimates using the logistic regression model are presented. Most of the examined individuals admitted recent water contacts (90.6% of the cases). The most frequent reason for contact was swimming, playing and fishing and the preferential site of contact was the river. According to the logistic regression technique, the main risk factors for infection were: a) water contact through swimming, playing and fishing; b) fording; c) bad hygiene. We concluded that recreational activities are the main reasons for schistosomiasis transmission in Pedro de Toledo and leisure alternatives should be offered to the local population.

Controle da esquistossomose mansônica em área de baixa transmissao

The schistosomiasis is transmitted by Biomphalaria tenagophila in our study area (Pedro de Toledo, São Paulo, Brazil). From 1980 to 1990 epidemiological surveys in a population of 4,000 inhabitants, has shown that: prevalences by Kato-Katz (KKT), immunofluorescence (FT) and intradermal (IDT) techniques were 22.8%, 55.5% and 51.8%, respectively; intensity of infection was low, 58.5 eggs per gram of faeces (epg); there were no symptomatic cases; prevalences were higher in mates, children and rural zone; index of potential contamination was 57.5% in the age group 5 to 20 years; 2/3 of patients were autochthonous; cases were no-randomly aggregated; transmission was focal and only 0.4% of snails were infected; water contacts through recreation showed the most important odds ratio; knowledge, attitudes and practices were satisfactory. From the epidemiological findings a control programme was carried out: yearly faeces exams, chemotherapy, molluscocide, health education and sanitation. Thus, the prevalence decreased sharply to 3.3% and intensity of infection to 30.3 epg; the incidence rates ranged between 0.4% and 2.5% annually; the sanitation became better and the youngsters were the main target in prophylaxis. To improve control, immunodiagnosis has to be conducted and the involvement of the population should be increase. However, we cannot forget that re-infection, therapeutic failure, etc, could play a major role in the maintenance this residual prevalence.The schistosomiasis is transmitted by Biomphalaria tenagophila in our study area (Pedro de Toledo, Sao Paulo, Brazil). From 1980 to 1990 epidemiological surveys in a population of 4.000 inhabitants, has shown that: prevalence Kato-Katz (KKT), immunofluorescence (FT) and intradermal (IDT) techniques were 22.8%, 55.5% and 51.8% respectively; intensity of infection was low, 58.5 eggs per gram of faeces (epg); there were no symptomatic cases; prevalences were higher in mates, children and rural zone; index of potential contamination was 57.5% in the age group 5 to 20 years; 2/3 of patients were autochtonous; cases were no-randomly aggregated; transmission was focal and only 0.4% of snails were infected; water contacts through recreation showed the most important odds ratio; knowledge, attitudes and practices were satisfatory. From the epidemiological control findings a control programme was carried out; yearly faeces exams, chemotherapy, molluscocide, health education and sanitation. Thus, the prevalence decreased sharply to 3.3% and intensity of infection to 30.3 epg; the incidence rates ranged between 0.4% and 2.5% annualy; the sanitation became better and the youngsters were the main target in prophylaxis. To improve control, immunodiagnosis has to be conducted and the involvment of the population should be increase. However, we cannot forget that re-infection and the involvment of the population should be increase. However, we cannot forget that re-infection, therapeutic failure, etc, could play a major role in the maintnance this residual prevalence.

The epidemiology and control of schistosomiasis mansoni where Biomphalaria tenagophila is the snail host

Desde 1980, esta-se estudando a epidemiologia e o controle da esquistossomose mansonica no Municipio de Pedro de Toledo (Estado de Sao Paulo, Brasil). Em 1980 a prevalencia avaliada por exame de fezes (metodo de Kato-Katz) foi de 22,8%. Estatisticamente, ao nivel de 5%, nao houve diferenca nas prevalencias observadas nas zonas rural e urbana. A intensidade de infeccao foi baixa (media geometrica de 58,5 ovos por grama de fezes). As maiores prevalencias e intensidades de infeccao foram registradas na faixa etaria de 5 a 29 anos. Geralmente a transmissao da endemia verificou-se durante o lazer. Apenas 0,4% de B. tenagophila mostraram-se positivos para cercarias de S. mansoni. A maioria dos portadores era assintomatico. O programa de controle foi intensificado apos avaliacao dos dados de 1980, resultando em diminuicao acentuada da prevalencia de 22,8% em 1980 para 6%. Esta prevalencia residual vem se mantendo ate 1987. Agora iniciamos estudos para investigar as possiveis causas dessa prevalencia residual.

Suscetibilidade de biomphalaria glabrata, B. straminea e B. tenagophila a diferentes cepas de schistosoma mansoni

The susceptibility of 3 species of snails from, Brazil, B. glabrata (Minas Gerais - MG - and Sao Paulo - SP - States), B. tenagophila (SP) and B. straminea (SP) to experimental infection with 4 human (MAP, PTH VPH, and OuH) and 2 rodent (PTR and VPR both from SP) isolates of S. mansoni was studied. Snails of each species were exposed individually to 10 miracidia and observed during a 70 day experimental period for mortality, sporocyst development and number of snails shedding cercariae. The B. glabrata from MG -was found to be susceptible to MAP (MG) and 5 from SP (PTH, VPH, OuH, PTR and VPR). The B. glabrata from SP -was found to be susceptible to MAP, OuH and VPR. High mortalites were observed among B. glabrata from SP. The B. stramlnea was found to be susceptible to MAP (only sporocysts), OuH and VPR parasites; mortality rates were lower in this species of snail than in the other species tested. B. tenagophila from SP was found to be susceptible only to sympatric strains, but with low infection rates. The results indicate the importance of transmission of schistosome by human migration from Sao Paulo to other Brazilian areas.The susceptibility of 3 species of snails from, Brazil, B. glabrata (Minas Gerais - MG - and Sao Paulo - SP - States), B. tenagophila (SP) and B. straminea (SP) to experimental infection with 4 human (MAP, PTH VPH, and OuH) and 2 rodent (PTR and VPR both from SP) isolates of S. mansoni was studied. Snails of each species were exposed individually to 10 miracidia and observed during a 70 day experimental period for mortality, sporocyst development and number of snails shedding cercariae. The B. glabrata from MG -was found to be susceptible to MAP (MG) and 5 from SP (PTH, VPH, OuH, PTR and VPR). The B. glabrata from SP -was found to be susceptible to MAP, OuH and VPR. High mortalites were observed among B. glabrata from SP. The B. stramlnea was found to be susceptible to MAP (only sporocysts), OuH and VPR parasites; mortality rates were lower in this species of snail than in the other species tested. B. tenagophila from SP was found to be susceptible only to sympatric strains, but with low infection rates. The results indicate the importance of transmission of schistosome by human migration from Sao Paulo to other Brazilian areas.

IgM-Immunofluorescence Test as a Diagnostic Tool for Epidemiologic Studies of Schistosomiasis in Low Endemic Areas

The high sensitivity and the ability to diagnose schistosomiasis in a very early phase after infection have indicated the detection of IgM antibodies to Schistosoma mansoni gut antigens by the immunofluorescence test (IgM-IFT) as a useful serological test for epidemiological studies in low endemic areas. When applied in a follow-up study for two years, higher rates of seroconversion from IFT negative to positive were observed during the summer months, suggesting seasonal transmission of schistosomiasis in the rural area of the municipality of Itariri (São Paulo, Brazil). In each survey, blood samples from about 600 schoolchildren were collected on filter paper and submitted to IgM-IFT. When the blood samples were classified for the IgM antibody levels, according to the intensity of fluorescent reaction observed at fluorescence microscopy, and correlated to the egg counts in the Kato-Katz positive patients, no association was observed. This observation might suggest that the intensity of fluorescence observed in the IgM-IFT, as an indicator of IgM antibody levels, could not be an useful seroepidemiological marker for classifying areas of low endemicity according to degrees of infection.