Distribution of schistosome infections in molluscan hosts at different levels of parasite prevalence.

Biomphalaria glabrata snails infected with Schistosoma mansoni were collected during consecutive seasons from a site in Brazil known to have a very high percentage of infected snails. Schistosoma mansoni cercariae from single snails were used to infect individual mice, and the recovered adult worms were genetically assessed using a mtVNTR marker. The number of unique parasite genotypes found per snail was compared to expected abundance values, based on the infection prevalence at the site, to determine the distribution of S. mansoni infections within the snail population. The observed distributions and those from previous studies were used to examine the relationship between schistosome prevalence and aggregation across a wide range of prevalence values. Our analysis showed that prevalence was inversely related to the degree of parasite overdispersion, and at high prevalence, S. mansoni infections were randomly distributed among snails.

Populational structure of Schistosoma mansoni assessed by DNA microsatellites.

DNA microsatellites were used as molecular markers to analyse the population structure of the laboratory LE strain and of 10 field isolates of Schistosoma mansoni, the aetiologic agent of schistosomiasis. Out of 16,000 DNA sequences analysed in databases, 622 microsatellite loci were identified in 481 sequences (3.0%). The AT repetitions were the most frequent, followed by AAT and AC. Six loci showing perfect repetitions were selected and used in the polymerase chain reaction to evaluate polymorphisms in the number of repeats. Two groups of worms were studied. The first group consisted of 78 individuals, 39 of each sex, of the LE strain. The second group of worms consisted of 10 field isolates: seven from humans and three from snails. Four of the six loci were polymorphic, containing 11-17 alleles per locus. No linkage disequilibrium was observed among loci and none of the loci was sex linked. In both groups of worms, a significant deviation from Hardy-Weinberg equilibrium was observed. The observed heterozygosity was always lower than the expected one. The polymerase chain reaction primers were S. mansoni specific. The LE strain showed a lower total number of alleles or a lower average number of alleles/polymorphic locus than the field isolates, suggesting that 41 years of laboratory maintenance exerted selective pressure on the LE strain. The S. mansoni populations from the field were most genetically undifferentiated (R(ST)<0.027), suggesting a high gene flow among them. Our results showed the usefulness of microsatellites for population analysis of S. mansoni, offering a new alternative for a better understanding of schistosomiasis epidemiology.

Apoptosis: a mechanism of immunoregulation during human Schistosomiasis mansoni.

People infected with schistosomes may present with a variety of clinical manifestations ranging from the relatively asymptomatic intestinal (INT) form to the hepatointestinal (HI) or hepatosplenic (HS) forms characterized by hepatomegaly and hepatosplenomegaly with severe portal hypertension, respectively. Flow cytometry analyses were used to evaluate the contribution of apoptosis in specific cell populations from schistosomiasis patients to the development of the different clinical forms of the disease. The results showed that cell death induced by combinations of specific antigen and cytokines corresponds with specific clinical presentations. It was shown that soluble egg antigen (SEA) increased the level of apoptosis only in T cells from INT patients. Stimulation with soluble lung worm antigen preparation (SLAP) did not induce significant differences in the levels of apoptosis in T cells from the patients with the different clinical forms of schistosomiasis. These results suggest for the first time that apoptosis plays an important role in the modulation of the anti-SEA response in INT patients.

CD4+ T cells of schistosomiasis naturally resistant individuals living in an endemic area produce interferon-gamma and tumour necrosis factor-alpha in response to the recombinant 14KDA Schistosoma mansoni fatty acid-binding protein.

Cellular immune responses to recombinant (r) Sm14 were examined in chronic, treated patients and uninfected individuals living in an endemic area for schistosomiasis. The lymphocyte proliferative responses and cytokine profile to this antigen were evaluated. Peripheral blood mononuclear cells (PBMC) of all groups studied proliferated to rSm14. However, the highest proliferation index to rSm14 was detected in uninfected endemic normal (EN) individuals who are naturally resistant to schistosomiasis. Regarding the cytokines produced, the levels of interleukin (IL)-5 and IL-10, known as Th2 cytokines, were not statistically different among all groups studied. In contrast, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha were produced in significantly higher amounts by PBMC of EN individuals following rSm14 stimulation. Additionally, we have determined by flow cytometry that CD4+ T cells from these individuals are the main lymphocyte subpopulation producing IFN-gamma and TNF-alpha. Moreover, we have used rIL-10 or rIFN-gamma, or monoclonal antibodies (MoAb) against these two cytokines to determine their role on cellular reactivity to rSm14. Exogenous IL-10 suppressed T-cell proliferation and neutralization of endogenous IL-10 restored lymphocyte activation and enhanced IFN-gamma and TNF-alpha production in chronically infected patients. In contrast, the addition of anti-IFN-gamma totally abrogated the PBMC proliferation within the EN group. This study demonstrated that IL-10 is an important cytokine down-regulating T-cell responses in chronic schistosomiasis, whereas lymphocyte proliferation in the uninfected resistant group is dependent on IFN-gamma. Taken together these results suggest that Th1 type of immune response induced in EN individuals to a specific schistosome antigen might be associated with resistance to infection and also highlighted the importance of Sm14 as a potential vaccine candidate.

[An alternative model for schistosomiasis control with active participation by the population through the Unified Health System (SUS) in Taquaraçu de Minas (Minas Gerais, Brazil) from 1985 to 1995]. / Participação popular no controle da esquistossomose através do Sistema Unico de Saúde (SUS), em Taquaraçu de Minas, (Minas Gerais, Brasil), entre 1985-1995: construção de um modelo alternativo.

This study evaluated the schistosomiasis control program implemented in Taquaraçu de Minas, Minas Gerais, from 1985 to 1995. In 1995, we measured the prevalence and intensity of infection for a retrospective comparison with the data from 1985. The local health team was trained to manage all the program activities. The work involved stool tests (Kato-Katz), selective specific treatment, medical care for patients spontaneously visiting the local health center, definition of measures to be adopted, and popular education focusing on information about the endemic disease. The safe drinking water supply covered 97% of the households in the county seat. Prevalence of infection between 1985 and 1995 was reduced 7.0 fold, from 30.9% to 4.3%. Intensity of infection was also reduced significantly, from 91.2 +/- 6.1 to 30.7 +/- 2.5 by the end of the program. Municipalization of the schistosomiasis control program through the SUS, by using selective treatment, intradomiciliary supply of potable water, medical care for patients spontaneously visiting the local health center, and popular education presented lasting results, indicating this model's feasibility for other endemic areas with similar characteristics.

[Schistosomiasis mansoni in urban territory. 2. A theoretical approach to the accumulation, concentration, and centralization of capital and the production of disease] / Distribuição da esquistossomose no espaço urbano. 2. Aproximação teórica sobre a acumulação, concentração, centralização do capital e a produção de doenças.

This study discusses the urbanization of schistosomiasis in the Greater Metropolitan Area of Belo Horizonte, Minas Gerais, Brazil. The observation that schistosomiasis has become endemic in an urban area is discussed using the concept of social organization of space as an exercise in providing an operational basis for the social and environmental paradigms of collective health. Elements from the new world economic order are discussed: the concept of socially constructed space, the internationalization of capital, the periphery, and the resulting collective disease generation process. Due to the deterioration of state health services and the logic of the new world economic order, the need for local schistosomiasis control solutions is stressed.

[Schistosomiasis mansoni occurrence in urban territory. 1. A case study of a peripheral urban area in Belo Horizonte, Minas Gerais, Brazil] / Distribuição da esquistossomose no espaço urbano. 1. O caso da região metropolitana de Belo Horizonte, Minas Gerais, Brasil.

This article characterizes the etiological conditions for schistosomiasis mansoni in the urban portion of the Greater Metropolitan Area of Belo Horizonte, Minas Gerais. Knowledge about this endemic disease is discussed with a clinical focus on subjects who lived in endemic areas from 1946 to 1994, taking into account the specific indicators for the endemic disease according to the measures adopted in its control.

Control of schistosomiasis mansoni in Ravena (Sabará, state of Minas Gerais, Brazil) through water supply and quadrennial treatments.

In this study, the results obtained in a control programme of schistosomiasis in Ravena (Sabará, Minas Gerais) between 1980 and 1992 are evaluated. Control measures used in this programme were: specific treatment of the people infected with Schistosoma mansoni at four year-intervals (1980/84/88) and the supply of tap water to 90% of the residences in 1980. A significant reduction of the prevalence (36.7% to 11.5%, p < or = 0.05) and of the intensity of the infection (228.9 eggs per gram of feces (epg), s = 3.7 to 60.3 epg, s = 3.5, p < or = 0.05) was observed. No cases of the severe form of the disease were diagnosed in the area. Factors independently associated with the infection were in 1980 daily sand extraction and the lack of tap water in residences and in 1992 daily sand extraction and fishing and weekly swimming. Concluding, the supply of tap water together with quadrennial treatments significantly diminished both the prevalence and intensity of the S. mansoni infection, with the additional gain of persistent low indices even after four-year intervals between the treatments.

[Alternative approaches to the control of schistosomiasis: trying to include subjective elements in epidemiology] / Abordagens alternativas no controle da esquistossomose: buscando incluir o subjetivo na epidemiologia.

This study discusses the possibility of integrating the "subjective" in epidemiological research. Alternative approaches are presented for programs to provide health and educational services, as well as others which are the right of citizens to receive and the responsibility of the government to provide. The characteristics of participatory research, community-based epidemiology, and popular education programs are described, with the purpose of constructing a model for the control of schistosomiasis using alternative methodologies, including in the model the perceptions and life styles of populations exposed to Schistosoma mansoni. The Federal Government is indicated as the institution to provide the material conditions necessary to form a citizenry with the collective will to control schistosomiasis.

[Environmental and social determinants in schistosomiasis mansoni in Ravena, Minas Gerais, Brazil]. / Determinantes ambientais e sociais da esquistossomose mansoni em Ravena, Minas Gerais, Brasil.

This study identified the role of biological and social determinants in the transmission of schistosomiasis mansoni in Ravena, Minas Gerais, Brazil, in 1980. This data was used to characterize the clinical and epidemiological profiles of the endemic desease in the population, allowing for the determination of the efficacy of the potable water supply and the specific treatment of those infected with S. mansoni. The district contains three locations, Ravenopolis, Ravena and Lavapes, where the prevalence of the endemic disease was, 20.1%, 42.6% and 63.9%, respectively. The prevalence in the district was statistically higher in men. The age brackets that displayed differences by gender were 10-14 and 15-19 years. Severity of infection was statistically different among individuals within the 10-14 year bracket in ali three locations, and in the 15-19 year bracket among individuals from Ravenopolis and Ravena. The hepatointestinal form was associated with age, and individuals under 15 years of age presented risk of infection 8.85 times higher than adults. Multivariable analysis of the factors involved in transmission of the disease showed that Lavapes was independently associated with infection. In that area, poor sanitary conditions and the proximity of houses to streams infested with S. marsoni cercariae facilitated infection of neighborhood women while performing domestic activities, as well as men digging sand from the streams for construction. These results show the focal nature of transmission of the endemic requiring specific intervention for effective control of disease.

[The use of risk factor determination for schistosomiasis in endemic areas in Brazil]. / Uso do paradigma de risco para a esquistossomose em áreas endêmicas no Brasil.

This study shows the results of risk factor determination for infection with Schistosoma mansoni in endemic areas in Brazil. An association was observed between infection with S. mansoni and a number of general conditions: absence of drinking water in the home, low individual income, illiteracy, and residence in an endemic area for more than five years. In addition to these conditions there was also association with a number of habits (risk factors): agricultural and domestic activities in open water supplies, swimming, and fishing. Analysis of the general conditions that may determine these risk factors indicated that provision of drinking water in the home and access to treatment are basic measures that could be adopted in many cases in order to prevent or control the morbidity of the disease. The efficacy of the use of risk factor determination for indication of control measures for this disease is questioned.

Identification of factors and groups at risk of infection with Schistosoma mansoni: a strategy for the implementation of control measures?

A fourteen year schistosomiasis control program in Peri-Peri (Capim Branco, MG) reduced prevalence from 43.5 to 4.4%; incidence from 19.0 to 2.9%, the geometric mean of the number of eggs from 281 to 87 and the level of the hepatoesplenic form cases from 5.9 to 0.0%. In 1991, three years after the interruption of the program, the prevalence had risen to 19.6%. The district consists of Barbosa (a rural area) and Peri-Peri itself (an urban area). In 1991, the prevalence in the two areas was 28.4% and 16.0% respectively. A multivariate analysis of risk factors for schistosomiasis indicated the domestic agricultural activity with population attributive risk (PAR) of 29.82%, the distance (< 10m) from home to water source (PAR = 25.93%) and weekly fishing (PAR = 17.21%) as being responsible for infections in the rural area. The recommended control measures for this area are non-manual irrigation and removal of homes to more than ten meters from irrigation ditches. In the urban area, it was observed that swimming at weekly intervals (PAR = 20.71%), daily domestic agricultural activity (PAR = 4.07%) and the absence of drinking water in the home (PAR = 4.29%) were responsible for infections. Thus, in the urban area the recommended control measures are the substitution of manual irrigation with an irrigation method that avoids contact with water, the creation of leisure options of the population and the provision of a domestic water supply.(ABSTRACT TRUNCATED AT 250 WORDS)

A 13-year follow-up of treatment and snail control in an area endemic for Schistosoma mansoni in Brazil: incidence of infection and reinfection.

The incidences of Schistosoma mansoni infection and reinfection were investigated in an endemic area of Brazil (Peri-Peri, State of Minas Gerais) where chemotherapy and snail control had been used for 13 years (1974-87). Two cohorts were followed: the first consisted of 584 individuals with no evidence of infection at entry (infection cohort), and the second comprised 296 individuals who were treated and did not eliminate eggs 8-12 months afterwards (reinfection cohort). The incidence of infection (per 100 person-years) decreased from 7.5 in 1974-77 to 3.6 in 1986-87, and that of reinfection from 21.3 in 1974-77 to 3.7 in 1986-87. Calendar period, age at risk, and sex were independently associated with both infection and reinfection, while a heavy S. mansoni egg count prior to treatment (> or = 500 epg (eggs per gram of stools)) was independently associated with reinfection. The geometric mean number of eggs after treatment among those reinfected (47 epg) was approximately half that among those infected for the first time (81.5 epg). Age at risk had the greatest effect on both infection and reinfection. The rate ratios of infection and reinfection were 3 to 6 times higher among individuals younger than 20 years than among those aged > or = 25 years, even after adjusting for confounders. This suggests the existence of a strong protective effect with increased age (because of biological and/or environmental factors) for both infection and reinfection.

PIP: Between 1974 and 1987 in Peri-Peri, Capim Branco Municipality, Minas Gerais State in Brazil, the schistosomiasis control program conducted a snail surveillance every 2-6 months, collected stool samples from village members annually, and administered oxamniquine to every person with Schistosoma mansoni eggs in their stool. Incidence of S. mansoni infection and reinfection steadily fell (from 7.5 to 3.6/100 person-years and from 21.3 to 3.7/100 person-years, respectively; p .001). Males were more likely to be infected or become reinfected than females (9.3 vs. 4.8, p .001 and 12.3 vs. 8, p = .025, respectively). 5-9 and 10-14 year olds had the highest incidence of S. mansoni reinfection (24.2 and 21.2 vs. 15.3 for 15-19 year olds, p .001, respectively). Infection rates were highest in 10-14 and 15-19 year olds (15 and 13.8 vs. 3.1-10.1 for 0-4 and 5-9 year olds, p .001, respectively). Reduced water contact and/or increased resistance/immunity may have accounted for lower infection and reinfection rates in people older than 20 years old. Infected people whose stool had a least 500 S. mansoni eggs/gm (epg) of stools were more likely to become reinfected faster and more frequently than people who had less than 500 epg (rate ratio, 1.7; p .001). Mean number of eggs was lower in the reinfected cohort than in the infected cohort (47 vs. 81.5 [ranges, 12-1320 vs. 12-5544]; p .001), suggesting that treatment protected against heavy reinfections. People whose egg count was at least 500 epg before treatment and were at least 25 years old did not become reinfected at a greater rate, however, further supporting the protective effect of age. These results showed that calendar period, age at risk, and sex were each associated with infection and reinfection and that a heavy egg count before treatment was independently associated only with reinfection.

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.

The prolonged use of niclosamide as a molluscicide for the control of Schistosoma mansoni.

Applications of niclosamide at three-monthly intervals were undertaken for 14 years in foci of Biomphalaria glabrata in the water sources of Peri-Peri (Capim Branco, MG). All the residents of the area were submitted to an annual fecal examination (Kato/Katz) and those individuals eliminating Schistosoma mansoni eggs were treated with oxamniquine. A malacological survey was undertaken at three-monthly intervals by means of ten scoops with a perforated ladle each ten metres along the two banks of the ditches and streams of the region. Where snails were found, molluscicide was applied by means of dripping or aspersion using a 3 ppm aqueous suspension of niclosamide. Initially, a mean of 14.3% of snails in the region were found to be eliminating cercariae. Following the first four applications of molluscicide, this was reduced to 0.0% and maintained at about 1.5% throughout the program. Thus, there was a continued possibility of schistosomiasis transmission in the area and it was observed that the population of snails reestablished itself within three months of molluscicide application. The results obtained in this study do not encourage the continual use of niclosamide as the only method of control of schistosomiasis.

Efficacy of alternating therapy with oxamniquine and praziquantel to treat Schistosoma mansoni in children following failure of first treatment.

Two hundred children infected with Schistosoma mansoni were treated with either 20 mg/kg oxamniquine or 60 mg/kg praziquantel. Cure rates (about 85%) were similar as was the percentage reduction (80%) in egg counts in uncured children. Treatment with the alternative drug of children not cured with the first treatment resulted in negative stools in 11 of 12 cases examined one month after the second round of therapy. In order to minimize the risk of the development of drug resistance, our data suggest that infected patients be treated with one drug, and therapeutic failures with another. Evidence from experiments in mice with isolates obtained after failures of one treatment in children suggests that therapeutic failure does not necessarily indicate the presence of drug-resistant schistosomes. The value of using mice to assess drug resistance in schistosomes is questioned.