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.

A partir de um estudo de caso-controle por pareamento (1:1) foram determinados os fatores de risco para infecção por Schistosoma mansoni. O trabalho foi desenvolvido no município de Pedro de Toledo, São Paulo, Brasil, área onde Biomphalaria tenagophila é o hospedeiro intermediário. Por meio de questionários foram obtidas informações sobre o padrão de contato com águas naturais; percepção da doença e condições sanitárias e socio-econômicas. Os fatores de risco foram estimados individualmente e através de modelo logístico. A maioria dos pesquisados admitiu contatos recentes com águas naturais (90,6% dos casos). O motivo mais freqüente para estes contatos foi nadar, brincar e pescar. O rio representou o principal local de contato com águas naturais. De acordo com a técnica de regressão logística, os principais fatores de risco foram: a) contato com água para nadar, brincar, pescar; b) vadear; c) más condições de higiene. Concluímos que as atividades recreativas são as principais responsáveis pela transmissão da esquistossomose em Pedro de Toledo e alternativas de lazer devem ser oferecidas a esta população.

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 pratices (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.

The susceptibility of four isolates of Schistosoma mansoni (BH, MAP, MPR-1 and K) to four multiple doses of anti-schistosomal agents (hycanthone, niridazole, oxamniquire, 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 praziquantel. 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 of three schistosomicides and demonstrate that the resistance of these isolates are stable over long periods of time without exposure to drugs.

Dentre as regiões do Estado de São Paulo, onde Biomphalaria tenagophila é hospedeira intermediária, o vale do Ribeira é área endêmica da esquistossomose. Nos últimos onze anos a endemia vem sendo intensamente controlada no vale, principalmente, nos municípios de Pedro de Toledo e Itariri. Estudamos a suscetibilidade de B. tenagophila de Itariri à linhagem simpátrica de Schistosoma mansoni, isolada do campo em 1988 e mantida no laboratório em camundongos suiço e B. tenagophila. Estudou-se a 2ª geração do trematódeo. Constituiram-se 3 grupos de 60 moluscos cada, sendo um grupo exposto a um miracídio e outro a 10 e um grupo controle não infectado. Observou-se mortalidade e eliminação de cercárias durante 78 dias. Findo este período, foram seguidos apenas moluscos que liberaram larvas até cessar sua eliminação. Nos moluscos expostos a 1 e 10 miracídios as mortalidades foram de 23% e 31% e os índices de infecção de 8% e 60% respectivamente, assim como a eliminação de cercárias foi de 82 e 104 dias. No controle a mortalidade foi de 22%. Assim, podemos concluir que B. tenagophila apresenta boa adaptação a linhagem simpátrica de S. mansoni

In the São Paulo State, Brazil, where the Biomphalaria tenagophila is the intermediate host, the Ribeira Valley is an important endemic schistosomiasis mansoni area. During last eleven years there has been intense control measures focusing on schistosomiasis. The efforts have been concentrated in the municipalities of Pedro de Toledo and Itariri. We determined the susceptibility of B. tenagophila to sympatric strain of S. mansoni, both recently isolated from Itariri field. In 1988, this strain was isolated and maintained in the experimental model: Swiss mice - sympatric B. tenagophila. The second generation of the worm was evaluated. The snail were divided in the three groups of 60 snails each. One group was exposed to 1 miracidium and other to 10. The third group was the control. The mortality and the shedding of cercariae were checked during 78 days. After that, the positive snails were observed until they ceased to shed cercariae. The exposed molluscs showed mortality rates of 23% and 31% and infection indexes were of 8% and 60% to 1 and 10 miracidia respectively. The mortality was of 22% in the control group. The periods of shedding cercariae in the two groups were 82 and 104 days. We can conclude that B. tenagophila is an effective intermediate host to the sympatric strain of S. mansoni sympatric strain

The objective of this study is to determine whether various hycanthone resistant strains of schistosomes which have been independently isolated are all affected in the same gene. A strain obtained from a Brazilian patient was compared with a strain of Puerto Rican origin selected in the laboratory. If the mutation conferring resistance involved two different genes, one would expect that the progeny of a cross between the two strains would show complementation, i.e. it would be sensitive to the drug. We have performed such a cross and obtained F1 hybrid worms wich were essentially all resistant, thus suggesting that the mutation conferring resistance in the two strains involves the same gene.

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.

Este trabalho foi realizado no município de Pedro de Toledo, no Estado de São Paulo, Brasil, em 1987 para esclarecer aspectos sobre níveis de transmissão ao homem de Schistosoma mansoni, quando o hospedeiro intermediário é Biomphalaria tenagophila. Desde 1980 vem sendo desenvolvido um programa de controle neste município. Foram submetidos a exames de fezes (método de Kato-Katz) 4.719 indivíduos das zonas rural e urbana. A taxa de prevalência foi de 4,8%, sendo maior nos homens (6,2%) e também na zona rural (5,8%). Foi de 35,1% a média de ovos de S. mansoni por grama de fezes (epg). Cerca de 80,0% dos portadores apresentavam menos de 100 epg e somente 20 indivíduos (9,0%) eliminavam mais do que metade do total de ovos. Os mais altos índices de potencial de contaminação (IPC) ocorreram nos grupos etários de 5 a 20 anos (57,6%). Dois terços dos pacientes investigados (207) eram autóctones de Pedro de Toledo. A distribuição geográfica dos portadores demonstrou evidente agregação dos casos autóctones, assim como uma íntima associação entre locais de contato da população com os criadouros de B. tenagophila. Este estudo demonstra que os portadores de S. mansoni não estão agregados ao acaso, que os jovens devem ser o principal objetivo na profilaxia, e que o programa de controle foi eficaz.

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.

Desde 1980, está-se estudando a epidemiologia e o controle da esquistossomose mansônica no Município de Pedro de Toledo (Estado de São Paulo, Brasil). Em 1980 a prevalência avaliada por exame de fezes (método de Kato-Katz) foi de 22,8%. Estatisticamente, ao nível de 5%, não houve diferença nas prêvalencias observadas nas zonas rural e urbana. A intensidade de infecção foi baixa (média geométrica de 58,5 ovos por grama de fezes). As maiores prevalências e intensidades de infecção foram registradas na faixa etária de 5 a 29 anos. Geralmente a transmissão da endemia verificou-se durante o lazer. Apenas 0,4% de B. tenagophila mostraram-se positivos para cercárias de S. mansoni. A maioria dos portadores era assintomático. O programa de controle foi intensificado após avaliação dos dados de 1980, resultando em diminuição acentuada da prevalência de 22,8% em 1980 para 6%. Esta prevalência residual vem se mantendo até 1987. Agora iniciamos estudos para investigar as possíveis causas dessa prevalência residual.

The epidemiology and control of schistosomiasis mansoni in the Municipality of Pedro de Toledo (State of S. Paulo, Brazil) since 1980, has been studied. In 1980 the prevalence evaluated by stool exams (Kato-Katz method) was 22.8% and no statistical difference at 5.0% level was observed between rural and urban zones. The intensity of infection was low (58.5 eggs/g of faeces); the highest prevalence and intensity of infection rates were observed within the group of from 5 to 29 years of age, respectively. The transmission of schistosomiasis usually occurred during leisure time. The majority of the carriers of the parasite were asymptomatic. Of the B. tenagophila examined only 0.4% were found to be infected. The control programme has been intensified from 1981 on resulting in a sharp decrease in the prevalence from 22.8% in 1980 to 6% at the present time. This result shows that, in spite of the control programme there is a residual human prevalence. A beginning has been made on the investigation into the possible causes of this residual prevalence (6.0% was maintained through out 1987).

Desde 1980, está-se estudando a epidemiologia e o controle da esquistossomose mansônica no Município de Pedro de Toledo (Estado de São Paulo, Brasil). Em 1980 a prevalência avaliada por exame de fezes (método de Kato-Katz) foi de 22,8%. Estatisticamente, ao nível de 5%, não houve diferença nas prêvalencias observadas nas zonas rural e urbana. A intensidade de infecção foi baixa (média geométrica de 58,5 ovos por grama de fezes). As maiores prevalências e intensidades de infecção foram registradas na faixa etária de 5 a 29 anos. Geralmente a transmissão da endemia verificou-se durante o lazer. Apenas 0,4% de B. tenagophila mostraram-se positivos para cercárias de S. mansoni. A maioria dos portadores era assintomático. O programa de controle foi intensificado após avaliação dos dados de 1980, resultando em diminuição acentuada da prevalência de 22,8% em 1980 para 6%. Esta prevalência residual vem se mantendo até 1987. Agora iniciamos estudos para investigar as possíveis causas dessa prevalência residual.

The epidemiology and control of schistosomiasis mansoni in the Municipality of Pedro de Toledo (State of S. Paulo, Brazil) since 1980, has been studied. In 1980 the prevalence evaluated by stool exams (Kato-Katz method) was 22.8% and no statistical difference at 5.0% level was observed between rural and urban zones. The intensity of infection was low (58.5 eggs/g of faeces); the highest prevalence and intensity of infection rates were observed within the group of from 5 to 29 years of age, respectively. The transmission of schistosomiasis usually occurred during leisure time. The majority of the carriers of the parasite were asymptomatic. Of the B. tenagophila examined only 0.4% were found to be infected. The control programme has been intensified from 1981 on resulting in a sharp decrease in the prevalence from 22.8% in 1980 to 6% at the present time. This result shows that, in spite of the control programme there is a residual human prevalence. A beginning has been made on the investigation into the possible causes of this residual prevalence (6.0% was maintained through out 1987).

Com duas linhagens de Biomphalaria glabrata foi estudada a suscetibilidade de cinco cepas de Schistosoma mansoni resistentes e suscetíveis a esquistossomicidas. Três cepas do trematódeo oriundas de Porto Rico apresentaram desenvolvimento mais lento e menor índice de infecção em B. glabrata brasileira quando comparados com o comportamento de duas cepas de S. Mansoni provenientes do Brasil. Por outro lado, as cepas brasileiras do parasita desenvolve ram bem e infectaram mais de 90% dos exemplares de B. glabrata portorriquenhos. Entre os resultados, ressalta-se que cepas resistentes a esquistossomicidas poderão ser introduzidas por pacientes em diferentes áreas geográficas como Brasil e Porto Rico.

Five strains of Schistosoma mansoni resistant and susceptible to schistosomicides were studied for infectivity of 2 strains of Biomphalaria glabrata one of Puerto Rican origin and the other of Brazilian origin. Puerto Rican strains of S. Mansoni developed more slowly and had a lower infectivity in Brazilian B. glabrata than did the Brazilian S. mansoni. However, Brazilian S. Mansoni developed as well in Puerto Rican snails as in Brazilian snails, indicating that drug resistant strains could easily be moved by travel of infected persons from one area to another.

Em condições experimentais foi estudada a suscetibilidade de Biomphalaria glabrata, B. straminea e B. tenagophila a quatro linhagens humanas (MAP, PTH, UPH, e OuH) e duas de roedores silvestres (PTR e VPR) do Schistosoma mansoni. Grupos de 50 moluscos foram expostos individualmente a 10 miracídios e observados durante 70 dias. Avaliou-se a suscetibilidade dos moluscos ao parasito por meio da % de animais com esporocistos, % de moluscos que eliminavam cercárias e mortalidade conjunta dos animais expostos e infectados. Exemplares de B. glabrata mineira infectaram-se com cepa simpátrica (MAP) e com 5 alopátricas do Estado de São Paulo (PTH, VPH, OuH, PTR e VPR). B. glabrata paulista mostrou altas taxas de infecção com as cepas MAP, VPR e OuH do trematódeo. Quatro % dos exemplares B. straminea de São Paulo eliminavam cercárias de cepas simpátricas; com cepa mineira apenas 4% apresentaram esporocistos na vigência de 20 miracídios por molusco; as menores taxas de mortalidade foram registradas com essa espécie de molusco, não sendo maior do que 20%. B. tenagophila paulista foi suscetível apenas às linhagens simpáticas sendo 6% a maior taxa de moluscos que eliminaram cercárias. Os resultados indicam que os movimentos populacionais humanos dentro do território paulista e para fora dele são importantes na disseminação da esquistossomose mansônica.

The susceptibility of 3 species of snails from, Brazil, B. glabrata (Minas Gerais - MG - and São 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 São Paulo to other Brazilian areas.

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.

No presente estudo, realizou-se uma tentativa de indução de resistência a 3 drogas esquistossomicidas em uma cepa brasileira de S. mansoni, segundo o esquema de indução de resistência tipo II preconizado por JANSMA et al. em 1977. Houve insucesso nas 3 tentativas realizadas. A geração parental tratada com a droga durante o estágio imaturo do verme mostrou-se menos suscetível aos quimioterápicos do que as gerações F1 e F2 do verme. Uma hipótese é levantada para a explicação do fato.

In this work, an attempt was made to induceng resistance to 3 schistosomicidal drugs in a Brazilian strain of S. mansoni, according to the Type II resistance induction scheme proposed by JANSMA et al. in 1977. Three attempts were unsuccessful. The parental generation treated with the drug during the immature stage of the worm was less susceptible to the chemotherapeutic agents than generations F1 and F2. A hypothesis is suggested as an explanation.

A suscetibilidade de linhagem brasileira (MAP), nas gerações F1 a F5 de S. mansoni a quatro drogas esquistossomicidas foi descrita em trabalho anterior. Na presente pesquisa os Autores testam a estabilidade da progênie F14 da referida linhagem às quatro drogas e a um novo medicamento, Oltipraz (35,972 RP). Cinco grupos de 12 camundongos infectados com cercárias por meio da imersão da cauda, foram tratados com hycanthone, oxamniquine, niridazole, praziquantel e Oltipraz. Foi utilizado um grupo controle de camundongos infectados e não tratados. A atividade esquistossomicida das drogas foi avaliada pela localização dos vermes no sistema porta, pelas alterações no oograma e percentagem de redução de vermes. A suscetibilidade dos vermes da geração F14 mostrou-se estável em relação àquelas observadas nas progênies F1 a F5; a progênie F14 de vermes foi resistente ao hycanthone e oxamniquine; todavia, for sensível ao niridazole, prazi- quantel e Oltipraz. Os Autores enfatizam a importância do fenômeno de resistência do verme em vista do fato do oxamniquine ser largamente utilizado em áreas do Brasil onde a esquistossomose mansônica é endêmica.

The susceptibility of the MAP Brazilian strain (F1 to F5 progenies) of S. mansoni to four antischistosomal drugs has been reported in a previous study. In the present investigation, progeny F14 of the same strain, was tested for stability to the same 4 drugs. A new medication, Oltipraz (35,972 RP), was added to the study. Five groups of 12 mice infected with cercariae by tail immersion were treated with hycanthone, oxamniquine, niridazole, praziquantel and Oltipraz. An untreated group was used as control. Schistosomal activity was assessed by the localization of worms in the portal vein system, by oogram changes, and percentage of parasite reduction. The stability of the susceptibility of progeny F14 did not change in relation to generations F1 to F5; the progeny was resistant to hycanthone and oxamniquine; but sensitive to niridazole, praziquantel and Oltipraz. We emphasize the importance of the phenomenon of resistance of the worm in view of the fact that oxamniquine has been widely used in Brazilian areas where mansonic schistosomiasis is endemic.

No período de janeiro de 1972 a agosto de 1975, nas margens da Represa de Americana (= Represa de Salto Grande), Brasil, em locais onde foi constatada a infecção por Schistosoma mansoni no homem e em Biomphalaria tenagophila, foram capturados 124 pequenos mamíferos: 44 exemplares de Cavia aperea aperea; 9 de Didelphis albiventris; 7 de Holochilus brasiliensis leucogaster; 39 de Lutreolina crassicaudata; 3 de Mus musculus brevirostris; 14 de Oryzomys nigripes eliurus; 1 de Oryzomys subflavus; 4 de Rattus rattus e 3 de Zygodontomys brachyurus. Verificou-se a infecção natural por S. mansoni em 2 exemplares de D. albiventris, em 3 de H. b. leucogaster e em 5 de L. crassicaudata. Estudou-se nestes animais a presença de elementos esquistossomóticos nas fezes e no intestino, bem como a distribuição e sexo de vermes adultos no sistema porta. Nas fezes de L. crassicuadata e de D. albiventris raramente foram observados ovos maduros do trematódeo. Em H. b. leucogaster era comum a presença destes elementos nas fezes. Devido a pequena abundância de H. b. leucogaster na área estudada, é provável que este roedor pouco contribua na disseminação de ovos de S. mansoni. Parece que a fauna de pequenos mamíferos estudada nesta região não desempenha papel relevante na manutenção do ciclo de S. mansoni.

124 small mammals around the Americana Reservoir (=Salto Grande Reservoir) were trapped during the period January, 1972 to August, 1975, in places where human and snail (Biomphalaria tenagophila) infections by S. mansoni have been recorded. The mammals included: 44 specimens of Cavia aperea aperea, 9 Didelphis albiventris, 7 Holochilus brasiliensis leucogaster, 39 Lutreolina crassicaudata, 3 Mus musculus brevirostris, 14 Oryzomys nigripes eliurus, 1 Oryzomys subflavus, 4 Rattus rattus and 3 Zygodontomys brachyurus. Two D. albiventris, 3 H. b. leucogaster and 5 L. crassicaudata were found naturally infected with S. mansoni. The presence of eggs was verified in feces and intestines and the worm burden was determined through recovery of schistosomes from mesenteric vessels and the hepatic portal system. The mature eggs of S. mansoni were rarely found in the feces of L. crassicaudata and D. albiventris although they were common in H. b. leucogaster. The low abundance of H. b. leucogaster in the study area probably indicates that this rodent contributes little to the dissemination of S. mansoni eggs. It does not appear that the small mammals in this region have an important role in maintaining the S. mansoni life cycle.