Am. J. Trop. Med. Hyg., 78(1), 2008, pp. 140-146
Copyright © 2008 by The American Society of Tropical Medicine and Hygiene
A Combined Strategy to Improve the Control of Schistosoma mansoni in Areas of Low Prevalence in Brazil
Martin Johannes Enk*,
Anna Carolina Lustosa Lima,
Cristiano Lara Massara,
Paulo Marcos Zech Coelho, AND
Virginia Torres Schall
Laboratory of Schistosomiasis, Department of Scientific Support—Unit for Biostatistics, Laboratory of Intestinal Helminthiasis, and Laboratory of Health Education, René Rachou Research Center/Oswaldo Cruz Foundation, Belo Horizonte, Minas Gerais, Brazil; Hospital Santa Casa de Misericordia de Belo Horizonte, Belo Horizonte, Minas Gerais, Brazil
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ABSTRACT
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Results of stool examinations for infections with Schistosoma mansoni among schoolchildren, living in a village of Minas Gerais State, Brazil, were used as an indicator to identify schistosomiasis-positive individuals within the entire population. This new approach is based on dividing the community into schoolchildren, members of households of schistosomiasis-positive and -negative schoolchildren, and members of households without schoolchildren. Each subgroup was evaluated comparing different sampling efforts with the predetermined "gold standard" to find the best relationship between detection rate and sampling effort. Consequently these results were combined, and a proposal for a new strategy, valid for an entire community, was elaborated. This alternative approach during the screening process permits to treat a similar proportion of positives as detected with 6 Kato–Katz slides of 3 stool samples, with 3-fold reduced sampling effort, enhancing the efficiency of schistosomiasis control programs in low-endemic areas.
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INTRODUCTION
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In Brazil, due to decades of successful application of control programs, the number of low-endemic areas increased significantly. Although morbidity and mortality of infections with Schistosoma mansoni were reduced progressively during this period, transmission continues nearly unchanged.1 This is confirmed by an increase of the geographical extension of the disease, the appearance of new foci and local outbreaks of acute schistosomiasis, especially in areas of rural tourism, which also indicates that surveillance and control of schistosomiasis in endemic areas with low prevalence remain problematic.2–4 Besides other factors, such as migration and insufficient sanitation infrastructure, lack of success seems also to be based on the diagnostic screening approach at the population level. The nationwide strategy currently applied—i.e., 1 Kato–Katz (KK) slide of a single stool sample—to determine infection rate, does not provide the necessary sensitivity and accuracy. Consequently, figures for prevalence in low-endemic areas are underestimated and not reliable.5 Studies carried out to develop more efficient diagnostic alternatives for the sustainable evaluation of prevalence and permanent epidemiologic surveillance did not result in a satisfactory solution for this problem. These alternative diagnostic tools are not cost-effective, do not show sufficient sensitivity, or are not easy to use under field conditions and at large scale.6 This study intends—in contrast to the research, which tries to develop new diagnostic tools—to improve the efficacy of the current diagnostic methodology, namely, the KK technique, by combining it with an approach based on an alternative screening strategy and epidemiologic data common in areas of low prevalence. The recently described approach to use results of stool examinations of schoolchildren as indicator for schistosomiasis-positive individuals in a community seems to be a promising methodology in this context.7 The current study tries to validate this methodology in a different setting and, beyond that, to develop a proposal of an improved strategy for the control and surveillance of schistosomiasis in low-endemic areas.
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MATERIALS AND METHODS
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Study area.
Chonim de Cima, a small town in the county of Governador Valadares, is located in the northeast of Minas Gerais state, Brazil. This location was selected because it is situated in an area of low prevalence for schistosomiasis and it offers the following favorable conditions: the population has never received treatment through the national schistosomiasis control program, the population size of 1,448 inhabitants was adequate for the study purpose, and school enrollment rate was > 90.0%, representing the Brazilian average. The study was carried out between 2005 and 2006.
The local economy is based on agriculture, cattle breeding, and small-scale regional trade. The area is characterized by multiple water sources, like brooks and small lakes, which are used for professional and leisure activities of the local population. The main brook of the area crosses the town and serves as principal recipient for untreated sewage.
Study population.
In cooperation with the local health authorities (PSF, Family Health Program), all residents (1,448) and their households (404) were registered. Nonpermanent residents (183) were excluded from this study, resulting in a total number of 1,265 participants. All 369 pupils > 6 years of age, attending the only school, located in the center of the town, participated in this project.
A subset of the population, denominated as the experimental group and representative for the general population, was selected to limit the enormous quantity of stool samples and stool examinations during the in-depth analysis of the infection rate for schistosomiasis. The sample size was calculated based on a test on comparison of proportions with a confidence level of 95.0% and a test power of 90.0%. The prevalence of 13.0% among schoolchildren, detected by a pilot study among 100 pupils, and an expected prevalence of 22.0% for the population with a size of 1,265 individuals were used to calculate the minimum sample size of 289 individuals. The selection process, designed as a systematic random sampling procedure, resulted in an experimental group consisting of 305 individuals living in 111 houses.
Parasitological survey.
After explaining the purpose of the project, the total population of 1,265 participants was screened for schistosomiasis by examining 2 slides of a single stool sample according to the KK technique.8 The stool samples for the experimental group consisting of 305 participants, collected during a 2-week period, were examined in the following manner: 6 slides of the first and 2 slides of the second and the third stool specimens, resulting in a total number of 10 slides for 3 stool specimens. A number of the 264 individuals of the experimental group returned a fourth stool sample, 66 of which provided enough material for 6 smears, 1 for 5 slides, 196 for 2 slides, and 1 for 1 slide. Furthermore, 0.5 g of each of 452 stool samples of the experimental group was processed by the formol–ether centrifugation technique according to Blagg and others,9 and the total sediment was examined. The sum of the results of all stool examinations of all samples of both techniques among the 305 participants served to establish the reference value of prevalence, which was called the "gold standard."
Technicians of the Laboratory of Schistosomiasis in the Rene Rachou Research Center/Fiocruz and the Secretary of Health for the State of Minas Gerais read all slides, and to ensure diagnostic efficacy, 10% of all slides were reexamined.
Study design.
In the first step, the approach to use schoolchildren as the indicator for schistosomiasis as described by Massara and others7 was reproduced in this study among the household members of the total population, to confirm its validity in another setting. In the second step, this methodology was combined with the results of increased sampling efforts, thus enabling development of a new strategy, which extends to an entire population and not only to the members of households of schoolchildren. For this purpose, the population of the experimental group was divided in 4 groups. The first consisted of all schoolchildren, the second of all participants without schoolchildren in their households. The third and fourth groups were stratified according to stool examination results of different sampling efforts among the schoolchildren, one group of members of households of schistosomiasis-positive schoolchildren and the other group of members of households of schistosomiasis-negative schoolchildren. Retrospectively, different combinations were designed by evaluating the different sampling efforts of each subgroup of the experimental group to identify and treat as many as possible schistosomiasis-positive individuals by using a minimum number of stool samples and slides, compared with the "gold standard" (Diagram 1
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DIAGRAM 1. Study design for the development of the improved strategy in detecting S. mansoni positives among the experimental group.
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Data analysis.
The 
2 test was used to compare proportions between groups. The odds ratio was used to determine the strength of association of results of stool examinations between groups of the population. The proportion of correctly detected individuals positive and negative for schistosomiasis of different sampling efforts in relation to the gold standard is denominated "efficacy" and expressed in percent (Tables 1 and 5). All tests were carried out with a 95.0% level of confidence. The software package MINITAB 14.0 was used to carry out these calculations.
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TABLE 1 Results in absolute numbers and percentage of schistosomiasis-positive and -negative individuals according to the increasing numbers of slides and stool samples in the experimental group*
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TABLE 5 Comparison of different combinations composed of varying sampling efforts among the four groups of the experimental group
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Treatment.
All participants positive for schistosomiasis were treated with praziquantel according to the recommendation of the Brazilian Ministry of Health (adults, 50 mg/kg in a single dose, children 
15 years old, 60 mg/kg in a single dose). Those positive for soil-transmitted helminthiasis (STH) (were treated with albendazole, both adults and children, 400 mg in a single dose) at the local health-care facility.10
Ethical considerations.
All participants were informed about the purpose of this study, the possible risks, and inconveniences. The study protocol was received and approved by the Ethical Review Board of the Réne Rachou Research Center/Fiocruz (No. 04/2005).
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RESULTS
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Parasitological survey.
According to the increase of the number of slides per stool sample and the number of stool samples, this study shows a steady increase of schistosomiasis-positive individuals among the total population and the experimental group. The prevalence in the total population ranges between 11.2% with 1 slide and 12.5% with 2 slides from the same sample, up to 20.8% considering all stool samples, including those of the in-depth analysis in the experimental group. In this study, a total of 263 schistosomiasis-positive individuals were identified among the 1,265 participants. Among the 305 participants of the experimental group, 42 individuals, corresponding to a prevalence of 13.7%, proved positive for schistosomiasis; by applying the same methodology as for the entire population, 47 individuals were identified, resulting in a prevalence of 15.4%. The experimental group was representative for the total population in relation to age (2 test; P = 0.147) and gender (2 test; P = 0.137). Furthermore, no statistically significant difference was found between the total population and the experimental group for the distribution of schistosomiasis-positive and -negative individuals, with data obtained through the examination of 2 slides of 2 stool samples according to the KK technique (2 test; P = 0.174). The detailed increase of prevalence according to the increased number of slides and stool samples of the in-depth analysis among the experimental group is shown in Table 1
. Our data for prevalence in the experimental group show that screening the population with 1 KK slide, which is the current approach recommended by the Brazilian Ministry of Health, misses 66 of the 108 positives (61.1%) compared with the numbers according to our "gold standard." Extrapolating these figures to the total population reveals totals of 448 (confidence interval, CI = 380–516) positive individuals and consequently 274 (CI = 249–298) undetected, and also untreated carriers of schistosomiasis, who maintain transmission of the disease in the area. The data also indicate that the sensitivity of such a strategy—KK examination of only 1 slide per stool sample—is only 38.9% with an efficacy of 78.4%.
Validation of the approach of using schoolchildren as indicators in another setting.
The results obtained by Massara and others could be confirmed by our data (Tables 2 and 3). There was no statistically significant difference in the proportion of the schistosomiasis-positive and -negative household members among the households of positive schoolchildren (2 test; P = 0.727 for the comparison with the total population, and P value = 0.079 for comparison with the experimental group). Although there was a statistically significant difference in the proportion among households with negative schoolchildren (2 test; P value = 0.040), evaluation of the odds ratios (ORs) in both studies shows a large amplitude of the 95.0% CI with a wide overlapping area, indicating significant similarity (our data—OR, 2.971; 95.0% CI = 1.384–6.381; data of Massara and others—OR, 4.684; 95.0% CI = 2.431–9.026).
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TABLE 2 Number and percentage of schistosomiasis positives and negatives detected in households of positive and negative schoolchildren found by Massara and others and our in study among the total population, using the same sampling effort of 2 slides of a single sample
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TABLE 3 Comparison of odds ratios found by Massara and others and our in study among the total population, using the same sampling effort of 2 slides of a single sample
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Evaluation of the approach at population level.
Because the experimental group is representative for the total population in age, gender, and distribution of schistosomiasis-positive individuals, this methodology was applied for all individuals of this group. The variability of the number of infected, detected by the KK technique depending on the number of slides per stool sample and number of stool samples, as well as the inclusion of the values for the "gold standard" revealed, as expected, increasing numbers in all 4 groups. These 4 groups are described above in the Material and Methods section "Study Design." Table 4 shows the figures for these groups in detail. Applying stratifications based on results obtained by examination of schoolchildren shows that the number of positives among the members of households of positive and negative schoolchildren increases with increases in the number of KK slides and samples.
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TABLE 4 Variability in the number of positives depending on the increase in the number of Kato–Katz slides and samples among 4 groups of the experimental population; results are shown in absolute numbers of positive individuals and in percentage of prevalence for each of the 4 groups
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On the basis of these data, a separate strategy for each of the 4 groups can be adopted, resulting in different combinations of these strategies. Each combination is characterized by the number of slides examined, as well as by specific values for prevalence, sensitivity, and efficacy. The figures for the different combinations are shown in Table 5. Combinations 8 and 13 increase the number of positives detected from 42 to 73 (73.8%) and from 42 to 69 (59.5%), respectively, with 2.2-and 1.8-fold increases in slides examined in relation to screening the entire population with 1 KK slide. In relation to 3 stool samples examined by 2 KK slides each, among the entire population, combinations 8 and 13 reveal insignificant reductions in the proportions of schistosomiasis-positive individuals of 2.0% and 3.9%, respectively, but considerably reduced sampling efforts (by 2.7- and 3.3-fold), which means 1,157 fewer slides for combination 8 and 1,270 fewer slides for combination 13 among the experimental group. Extrapolation of these figures to the total population means 4,799 fewer slides for combination 8 and 5,267 fewer slides for combination 13 (Table 6). Combinations 8 and 13 reveal themselves as the most effective options, considering the number of positives detected or treated in relation to the number of slides examined. These data are observed in Figure 1. Comparisons among the proportions of positives for each of the 2 combinations with the approach using 1 KK slide for the entire population (prevalence of 13.8%) show that there is significant difference in the proportion of positives detected (combination 8—prevalence of 23.9%, 2 test; P = 0.001; combination 13—prevalence of 22.0%, 2 test; P = 0.008). On the other hand, there is no statistically significant difference when both combinations are compared with the proportion of positives found by examining 3 stool samples with 2 KK slides each (proportion of positives, 25.9%: 2 test, combination 8, P = 0.574; combination 13, P = 0.255). Because the experimental group is representative for the total population, data for the combinations among the experimental group may be extrapolated to the total population. A selected set of these extrapolations are outlined in Table 6. In our setting, among the total population, this increased sampling effort (3 stool samples + two KK slides each) reveals a total number of 328 (CI = 265–390) positives detected and 120 (CI = 98–142) or 26.8% missed, indicating a significant improvement of the detection rate (2 test; P = 0.000) and of sensitivity and efficacy with values of 73.1% (CI = 68.1–78.1) and 90.5% (CI = 87.2–93.8), respectively.
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TABLE 6 Results for extrapolation of combinations at the population level, including the total number of Kato–Katz slides examined*
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DISCUSSION
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Our study supports the conclusions drawn by Massara and others, that there is an association between the infection rates of schistosomiasis among schoolchildren and their household members. Schistosomiasis-positive schoolchildren indicate, according to Massara and others, a 4 times—and according to our data—a 3 times higher probability to detect another positive individual living in the same household, compared with members of households of schistosomiasis-negative schoolchildren. The difference found in the direct comparison of the proportions of positive individuals among households of negative schoolchildren (2 test; P value = 0.040) is probably caused by the fact that Massara and others used a sample of households of schistosomiasis-negative schoolchildren 3 times as large as that of positive schoolchildren and not the entire population, as in our study, resulting in an underestimation of positive household members among the households of negative schoolchildren.
Our approach was then applied to the entire population, by using schistosomiasis-positive and -negative schoolchildren as indicators. This approach of categorizing an entire population resulted in division of this population into 4 distinctive groups with specific infection rates for each. In combination with in-depth analysis of the infection rate of each of the 4 groups, a new strategy was developed, which shows potential to improve the efficiency of the control of schistosomiasis in low-endemic areas.
An important point regarding schistosomiasis control in low-endemic areas is the fact that prevalence is severely underestimated.5 This is based on a lack of sensitivity of the diagnostic method and consequently causes a negative impact on the efficiency of control programs.11 Traditionally, to increase the sensitivity of the diagnostic method, it is recommended that the number of stool samples and KK slides examined per specimen be increased. There exists a general agreement that 3 stool samples examined by 2 KK slides each ensure solid and reliable figures for infection rates.12–14 Unfortunately, this approach is not sustainable because the increased sampling effort is not practicable at large scale under field conditions and the 6-fold increase of KK slides—in our study population, from 1,265 to 7,590 slides—results in an unaffordable increase in expenditures for mass screening. One solution to this dilemma is blanket mass treatment without prior screening, as suggested decades ago.15,16 The main problem regarding this option is the high number of unnecessary treatments, which in our setting results in 817 individuals, or 64.6% of the population. Although praziquantel is a relatively safe drug, causing few side effects, ethical considerations have to be taken into account if mass treatment under such circumstances is appropriate.
The other option, if improvement of schistosomiasis-control programs in low-endemic areas is the goal, lies in the combination of the diagnostic technique with an indirect approach which indicates the most-infected segments of the population. As mentioned above, screening of schoolchildren and using their stool examination results as indicators for identifying schistosomiasis-positive individuals among their household members, can provide this valuable information. In our setting, according to figures for the "gold standard" and including the schoolchildren into the households, rates of infection are 61.5% for households of positive schoolchildren, 14.5% for households of negative schoolchildren, and 35.7% for households without schoolchildren among the experimental group. These figures clearly show how the sampling effort should be directed to increase the efficacy of the screening method. Using the same figures, but excluding the schoolchildren, infection rates are observed to be 56.5% for households of positive schoolchildren and 31.9% for households of negative schoolchildren (Table 4). The finding that 1 segment of the population, namely, the household members of schistosomiasis-positive schoolchildren, revealed, according to the in-depth analysis, an infection rate > 50.0%, which constitutes another important pillar of this new strategy. Given this high infection rate, targeted mass treatment without prior screening is justified.10,17 Mass treatment of this segment also helps to limit the considerable number of stool examinations, resources for which can be used for other segments of the population to increase the detection rate.
Putting this model into practice means, first, to screen all schoolchildren with a relatively high sampling effort and to treat all those identified as positive for schistosomiasis together with all their household members. Next, all members of households without schoolchildren and those of schistosomiasis-negative schoolchildren are screened and treated as well. According to different sampling efforts, various combinations of the screening procedures can be designed (Table 5). Of these combinations, numbers 8 and 13 prove to be the most effective, considering the numbers of slides examined and the numbers of positives reached for treatment. Regarding the sampling effort, it is worth mentioning that both combinations require examination of more slides than the current approach (1 KK slide per person). The number of slides examined increases from 305 for 1 KK slide for all participants to 673 for combination 8 and to 560 for combination 13 among the experimental group, and from 1,256 for 1 KK slide for all participants to 2,791 for combination 8 and to 2,323 for combination 13 among the total population. Nevertheless, the increase in number of slides for combinations 8 and 13 is reasonable in comparison to 1,830 slides for 3 stool samples examined by 2 KK slides among the experimental group and 7,590 slides among the total population, which would be needed to reach the same detection rate as obtained by our method’s fewer slides.
Our data indicate that there is room for improvement of control strategies, even if the least sensible diagnostic procedure, KK examination of a single stool sample with one slide, is used selectively by combining it with a supportive approach, which would still provide information to direct the sampling effort. Furthermore, as this above-described new strategy focuses on schoolchildren for identification of schistosomiasis-positive individuals within a community, there is an opportunity to combine such a program with health-educational activities at the school and community levels, which also enhance the success of such a program through better adherence and compliance.18–20 School- and community-based control programs are known to provide mechanisms not only to engage the population but also make programs sustainable and maintainable by active participation of the community. Integration with other control programs, such as for STH, filariasis, and others, makes it possible to combine such programs, which consequently results in reduced costs for integrated programs.21,22
However, there are limitations to the suggested strategy, which are not only based on the specific conditions of our setting, but also on the requirement of a developed primary health-care structure, high school enrollment, and a solid family structure within the community, which shows similar water-contact patterns among household members. Most of these requirements are met for rural or semi-urban areas, especially in Brazil, and it was the case for our study area. Therefore, our findings may serve as a proposal for the improvement of schistosomiasis control in areas of low transmission.
Received March 23, 2007.
Accepted for publication September 24, 2007.
Acknowledgments: The authors thank Aureo Almeida de Oliveira, senior technician of the Laboratory of Schistosomiasis, for his valuable contribution in carrying out field work and examining stool samples. We are grateful for the excellent cooperation of the technical team of the Secretary of Health in the State of Minas Gerais, Section Governador Valadares.
Financial support: This work obtained financial support from the Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG), Brazil, Conselho National de Pesquisa (CNPq), and Sistema Único de Saúde (SUS).
* Address correspondence to Martin Enk, Hospital Santa Casa de Misericordia de Belo Horizonte, Belo Horizonte, Minas Gerais, Brazil. E-mail: marenk{at}cpqrr.fiocruz.br 
Authors’ addresses: Martin Johannes Enk and Paulo Marcos Zech Coelho, Laboratory of Schistosomiasis, René Rachou Research Center/Oswaldo Cruz Foundation, Av. Augusto de Lima 1715, Belo Horizonte, Minas Gerais, Brazil, Telephone: +55–31–33497700, Fax: +55–31–32953115, E-mail: marenk{at}cpqrr.fiocruz.br, coelhopm{at}cpqrr.fiocruz.br. Anna Carolina Lustosa Lima, Department of Scientific Support, Unit for Biostatistics, René Rachou Research Center/Oswaldo Cruz Foundation, Av. Augusto de Lima 1715, Belo Horizonte, Minas Gerais, Brazil, E-mail: anna{at}cpqrr.fiocruz.br. Cristiano Lara Massara, Laboratory of Helminthiasis, René Rachou Research Center/Oswaldo Cruz Foundation, Av. Augusto de Lima 1715, Belo Horizonte, Minas Gerais, Brazil, E-mail: massara{at}cpqrr.fiocruz.br. Virginia Torres Schall, Laboratory of Health Education, René Rachou Research Center/Oswaldo Cruz Foundation, Av. Augusto de Lima 1715, Belo Horizonte, Minas Gerais, Brazil, E-mail: vtschall{at}cpqrr.fiocruz.br.
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REFERENCES
|
- Katz N, 1998. Schistosomiasis control in Brazil. Mem Inst Oswaldo Cruz 93 (Suppl 1): 33–35.[Medline]
- Barbosa CS, Montenegro SML, Abat FG, Domingues AL, 2001. Specific situations related to acute schistosomiasis in Pernambuco, Brasil. Mem Inst Oswaldo Cruz 96 (Suppl 5): 169–172.[Web of Science][Medline]
- Enk MJ, Amorim A, Schall VT, 2003. Acute schistosomiasis outbreak in the metropolitan area of Belo Horizonte, Minas Gerais: alert about the risk of unnoticed transmission increased by growing rural tourism. Mem Inst Oswaldo Cruz 98 (Suppl. 6): 745–750.[Web of Science][Medline]
- Enk MJ, Caldeira RL, Carvalho OS, Schall VT, 2004. Rural tourism as a risk factor for the transmission of schistosomiasis in Mina Gerais, Brazil. Mem Inst Oswaldo Cruz 98 (Suppl 1): 105–108.
- De Vlaas SJ, Gryseels B, 1992. Underestimation of Schistosoma mansoni prevalences. Parasitol Today 8: 274–277.[Web of Science][Medline]
- Rabelo A, Enk MJ, 2007. Working Paper 8. Progress towards the Detection of Schistosomiasis. Scientific Working Group. Report on Schistosomiasis. Geneva: WHO. Available at: http://www.who.int/tdr/swg/07.
- Massara CL, Peixoto SV, Enk MJ, Barros HS, Carvalho OS, Sakurai E, Schall VT, 2006. Evaluation of an improved approach using residences of schistosomiasis-positive schoolchildren to identify carriers in an area of low endemicity. Am J Trop Med Hyg 74: 495–499.[Abstract/Free Full Text]
- Katz N, Chaves A, Pellegrino J, 1972. A simple device for quantitative stool thick-smear technique schistosomiasis mansoni. Rev Inst Med Trop Sao Paulo 14: 397–400.[Medline]
- Blagg W, Schoegel EL, Mansour NS, Khalat GI, 1955. A new concentration technique for the demonstration of protozoa and helminth eggs in feces. Am J Trop Med Hyg 4: 23–28.[Abstract/Free Full Text]
- Brazilian Ministry of Health, 2003. Manual for Public Health Workers: Schistosomiasis. Fourth edition. Belo Horizonte, Brazil: Ministry of Health—National Health Foundation.
- Kongs A, Marks G, Verle P, Van det Stuyft P, 2001. The unreliability of the Kato–Katz technique limits its usefulness for evaluation of S. mansoni infections. Trop Med Int Health 6: 163–169.[Web of Science][Medline]
- Rabelo ALT, Rocha RS, Oliveira JPM, Katz N, Lambertucci JR, 1992. Stool examination and rectal biopsy in the diagnosis and therapeutical evaluation of Schistosomiasis mansoni. Rev Inst Med Trop Sao Paulo 34: 601–608.[Web of Science][Medline]
- Engels D, Sinzinkayo E, de Vlas SJ, Gryseels B, 1996. Intraspecimen fecal egg count variation in Schistosoma mansoni infection. Am J Trop Med Hyg 54: 319–324.[Abstract/Free Full Text]
- Utzinger J, Booth M, N’Goran EK, Muller I, Tanner M, Lengeler C, 2001. Relative contribution of day-to-day and intraspecimen variation in faecal egg counts of Schistosoma mansoni before and after treatment with praziquantel. Parasitology 122: 537–554.[Medline]
- Engels D, Sinzinkayo E, de Vlas SJ, Gryseels B, 1997. Day-to-day egg count fluctuation in Schistosoma mansoni infection and its operational implications. Am J Trop Med Hyg 57: 571–577.[Abstract/Free Full Text]
- Almeida Machado P, 1982. The Brazilian program for schistosomiasis control, 1975–1979. Am J Trop Med Hyg 31: 76–86.[Abstract/Free Full Text]
- World Health Organization, 2000. Report of the WHO Informal Consultation on Schistosomiasis in Low Transmission Areas: Control Strategies and Criteria for Elimination. WHO/CDS/CPE/SIP/2001.1. Geneva: WHO.
- Schall VT, Dias AGP, Malaquias MLG, Gomes dos Santos M, 1993. Educação em saúde em escolas públicas de primeiro grau da periferia de Belo Horizonte, MG (Brasil). Avaliação de um programa relativo a esquistossomose. Rev Inst Med Trop Sao Paulo 35: 563–572.[Medline]
- Coura-Filho P, 1998. 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. Cad Saúde Púb 14: 111–122.
- Barbosa CB, Silva CB, Barbosa FN, 1996. Esquistossomose: reprodução e expansão da endemia no estado de Pernambuco no Brasil. Rev Saúde Púb 30: 609–616.
- Lammie PJ, Fenwick A, Utzinger J, 2006. A blueprint for success: integration of neglected tropical disease control programmes. Trends Parasitol 22: 313–321.[Web of Science][Medline]
- Brady AM, Hooper PJ, Otterson EA, 2006. Projected benefits from integrating NTD programs in sub-Saharan Africa. Trends Parasitol 22: 285–291.[Web of Science][Medline]
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ABSTRACT
INTRODUCTION
1 to