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Am. J. Trop. Med. Hyg., 75(2), 2006, pp. 278-286
Copyright © 2006 by The American Society of Tropical Medicine and Hygiene

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MORBIDITY INDICATORS OF SCHISTOSOMA MANSONI: RELATIONSHIP BETWEEN INFECTION AND ANEMIA IN UGANDAN SCHOOLCHILDREN BEFORE AND AFTER PRAZIQUANTEL AND ALBENDAZOLE CHEMOTHERAPY

ARTEMIS KOUKOUNARI*, ALAN FENWICK, SARAH WHAWELL, NARCIS B. KABATEREINE, FRANCIS KAZIBWE, EDRIDAH M. TUKAHEBWA, J. RUSSELL STOTHARD, CHRISTL A. DONNELLY, AND JOANNE P. WEBSTER
Schistosomiasis Control Initiative, Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, London, United Kingdom; Vector Control Division, Ministry of Health, Kampala, Uganda; Department of Zoology, Natural History Museum, London, United Kingdom; Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, London, United Kingdom


ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The potential relationship between Schistosoma mansoni and anemia was examined using data obtained by the Schistosomiasis Control Initiative (SCI) before (baseline) and 1 year after (follow-up) a chemotherapeutic treatment program in Uganda. Changes in hemoglobin (Hb) levels in 2,788 children in relation to their schistosomiasis and/or hookworm infection intensity category and baseline anemia status were analyzed. At baseline, significant predictors of childhood anemia were intensities of S. mansoni and hookworm infection. At follow-up, moderate or heavy hookworm as well as heavy S. mansoni infections were important. Children heavily infected with S. mansoni or hookworm had significantly lower Hb counts at baseline compared with those not infected. Among anemic children at the baseline survey, a significant increase in Hb counts of 0.834 g/dL after treatment was found. Our results suggest that anemia is associated with schistosomiasis and hookworm in Ugandan children and that such anemia shows a significant improvement after chemotherapy.


INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Anemia is a common problem throughout the world and of enormous public health concern in developing countries, but its etiology is very complex, making the effect of any one factor difficult to assess. Malaria plays a key causative role for anemia among young African children, although HIV infection, hemoglobinopathies, intestinal helminths, in particular that of hookworm infection, poor nutritional status, and micronutrient deficiencies are also likely to make important additional contributions.1 Schistosomiasis is a parasitic disease of profound medical and veterinary importance, second only to malaria in terms of parasite-induced human morbidity and mortality, with some 600 million people exposed and 200 million infected at any time throughout the tropical world.2 The relative role of schistosomiasis as a causative agent for anemia, however, particularly compared with that known for hookworm infection, remains controversial.3–7 Preston and Dargie,8 for instance, provided convincing evidence that schistosomiasis causes anemia in experimental animals; however, although Foy and Nelson9 did acknowledge that anemia was generally associated with heavy schistosome infections, they doubted that early or light infections were of importance. There is, nevertheless, a general consensus for the need for further epidemiologic research into the potential role of schistosomiasis as a causative agent for anemia.9,10

Since 2003, the Schistosomiasis Control Initiative (SCI) has assisted six sub-Saharan African countries with the objective to develop sustainable national schistosomiasis morbidity control programs and reach at least 75% of school-aged children and other high-risk group through mass deworming using praziquantel for schistosomiasis and albendazole for intestinal helminths. Such control programs thereby provide a unique opportunity to assess the potential role of schistosomiasis and/or other intestinal helminths as causative agents of anemia morbidity, together with the potential ameliorative impact of chemotherapy on a large scale. This may be particularly pertinent in terms of identifying and evaluating morbidity associated with S. mansoni (intestinal schistosomiasis), which is frequently very difficult to assess and quantify precisely except in the most severe or late chronic cases.11–14 Moreover, because demonstration of successful morbidity control is feasible only if there are reliable morbidity markers capable of showing reversion within the time frame of disease surveillance, it is vital to identify S. mansoni morbidity indicators for sustainable disease control and for evaluating the success of intervention.15,16

Using uniquely detailed data arising from the Ugandan National Schistosomiasis Control Program, before and 1 year after praziquantel and albendazole chemotherapy, we aimed to evaluate the potential relationship between S. mansoni infection, anti-helminthic chemotherapy, and anemia and to assess the extent to which schistosomiasis is a cause of anemia.


MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Study sites, sampling, and cohort design. Parasitological and morbidity data were collected on a cohort of 4,351 Ugandan children, 6–14 years old, randomly sampled from 37 schools situated in eight districts just before and one year after implementation (2003 and 2004, respectively), as part of ongoing monitoring and evaluations of the SCI program in Uganda. The eight districts were selected to represent the Albert Nile (Nebbi, Arua, and Moyo), Lake Victoria (Bugiri, Busia, and Mayuge) and Lake Albert basins (Masindi and Hoima). Further details on these districts and their inhabitants are provided elsewhere.17,18 Schools were chosen on the basis of existing S. mansoni data for schoolchildren from Uganda (SCI-National Survey of Bilharziasis) and parasitological stratification with different categories of infection prevalence, classified as low (< 10%), medium (11–50%), and high prevalence (> 50%) within each district, which also allowed pooling to reach sample sizes technically detailed in Brooker and others.19 Fixed cohort structure was recruited at each school to allow comparisons to be made across schools and districts. Required sample sizes were calculated using the EpiSchisto software tool (http://www.schoolsandhealth.org/epidynamics.htm) using an expected reduction in mean intensity of 60% (S. mansoni) after chemotherapy to achieve 80% statistical power and a significance level of 5%. The value of 60% was chosen as a conservative estimate of the expected reduction over a 2-year period (two annual treatments). An overall drop-out rate of 40% over the course of the monitoring period was also allowed.

As it was not logistically possible to survey all schools within the same month, surveys were staggered. Children were identified at follow-up using a named roll call as well as retrieval of SCI individual treatment cards with unique code identifier given to the children the previous year as well as hardcopy of a group cohort photograph to ensure that children remember to which group they were reassigned. Before the 1-year follow-up visit a pre-survey team re-registered the children and also sensitized the children to ensure that as many children as possible in the cohorts were at school the day of survey. All children enrolled into this study were interviewed and examined by appropriately trained Ministry of Health field workers. Administration of praziquantel and albendazole was according to WHO guidelines (praziquantel 40 mg/kg and single 400 mg albendazole tablet). Ethical clearance was obtained from the Ugandan National Council of Science and Technology and Imperial College London. For ethical reasons, it was not appropriate to include any untreated control groups in the study design.

Parasitological and anemia morbidity data. A single stool sample was collected from each individual and 41.7 mg was processed to make duplicate Kato-Katz slides for microscopic determination of schistosome and/or hookworm infection and, where applicable, egg per gram counts. For comparative reasons between the two successive years of study, where the second measurement of the Kato-Katz smear was missing, S mansoni prevalence and individual intensities were calculated using a single thick Kato-Katz smear, although we are aware that we miss a certain proportion of infections for assessment of individuals’ infection status, by this way. Anemia was defined (according to WHO guidelines), as a dichotomous variable taking the value 1 for children from 5 to 11 years old with Hb < 11.5 g/dL and for children between 12 and 14 years old with Hb < 12.0 g/dL. Further details for other indicators included and methodology followed in the SCI questionnaires are given elsewhere.19 All Kato-Katz smears were read within 1 hour of preparation so that hookworm eggs could be easily seen.

S. haematobium is known not to be endemic in these areas of Uganda.20 However, for absolute confirmation, urine from all children sampled was also tested for microhematuria using hemastix dipsticks and all urine sampled from children from the 11-year-old cohort was pooled for concentration of schistosome eggs using a Pitchford and Visser funnel and no S. haematobium egg was observed. We are therefore fully confident that S. haematobium was absent within this cohort. The prevalence of Trichuris trichura and Ascaris lumbricoides is unevenly distributed in the country with prevalence greatest in southwestern Uganda and such infections were also examined from the feces of all children sampled.21

Nutritional assessment data (i.e., weight and height) and blood samples for hemoglobin levels were obtained from each individual by the finger prick method, because this provides a sufficient sample for accurate Hb measurement using a Hemocue photometer.22

Statistical analyses. Because of clustered data with a natural hierarchical structure, we chose to use linear hierarchical models to model changes in Hb levels from baseline to follow-up and hierarchical logistic regression models to model the risk of being anemic. Additionally, because schistosomiasis occurs focally, heterogeneity in the degree of endemicity among schools has to be accounted for.23 In such circumstances, ordinary least squares regression can overestimate the precision associated with an analysis yielding spuriously statistically significant results (i.e., a type 1 error). Hierarchical models permit combination of exposures to group and individual factors that is important in epidemiologic analyses of infectious disease data.24,25

The hierarchical logistic regression models were fitted to data coming from children with complete records at each time-point of interest. Because of variable cohort recovery success, attributable to frequent population movements within Uganda, the remainder of the statistical analyses were restricted to children with complete records from both time-points of interest, and no replacements were used for missing subjects. Summary reportings, figures, and analyses are based on data from all available subjects. A comparison between the baseline characteristics of children successfully followed-up and those that dropped out in the second year of the study was performed through {chi}2 tests with regard to all the parameters examined in this study. Frequency tables were obtained using SAS V8 (SAS Institute, Cary, NC). A forward selection procedure was used for the evaluation of the remaining variables in the final models.

An association of anemia with parasitic infections (schistosome and hookworm) was studied after simultaneously adjusting for potential confounders in the statistical models used. Indices of the anthropometric status of the studied children based on the 1978 CDC/WHO growth reference curves were computed using the Nutstat program within Epi Info V 3.3. Body mass index is considered an indicator of acute under-nutrition (thinness or wasting) and is generally associated with failure to gain weight or a loss of weight.26–28 The Z-score cut-off point recommended by WHO, CDC, and others to classify low anthropometric levels is 2 SD units below the reference median for this specific index. Cut-off of -2 body mass index Z-scores (BMIZ) were calculated to classify underweight children and finally this categorical variable was incorporated in all models as a potential predictor. Initially we examined the impact of parasitic infections, sex, and nutritional status as defined from Z-scores at baseline and follow-up using two-level multivariate logistic regression models with level 1 (the children) and level 2 (the schools). We also tested three-level multivariate logistic regression models with level 3 (the districts), but it was proved that the districts were rather homogeneous in the risk of being anemic, and therefore this random effect was not finally included in the models. Nutritional status was included in the baseline hierarchical logistic regression model as generally malnutrition in children is the consequence of a range of factors that are often related to poor food quality, insufficient food intake, and severe and repeated infectious diseases, or frequently some combinations of the three. The same variable (BMI Z-score at baseline) was included in the hierarchical logistic regression model referring to 1-year post-praziquantel and albendazole treatment, because in this study, the duration of this period did not produce a nutritional impact. Finally, in both hierarchical logistic regression models the BMI Z-score at baseline was not significant, and therefore it was omitted from these models. Age was included in both hierarchical logistic regression models (baseline and follow-up) as a categorical variable.

Two separate hierarchical linear modeling analyses were carried out to determine any change in the children’s Hb levels in relation to their schistosomiasis and/or hookworm infection intensity category, controlling at the same time for age and sex and anemia status (as defined above). Children’s Hb levels at baseline and 1-year post-treatment were modeled through three-level hierarchical models where level 1 (two periods of interest), level 2 (the children), and level 3 (the schools). The validity of the distributional assumptions of this model was examined using plots of level 1, level 2, and level 3 residuals against their normal scores. To take into account the paired data structure, a dummy variable corresponding to the second year of study was included as a covariate in the model. Through this model we aimed to quantify the adjusted overall change of Hb from baseline to follow-up and to quantify average Hb counts of different groups of children at baseline.

Changes in Hb levels in relation to their baseline schistosomiasis and/or hookworm infection intensity category and anemia status from baseline to 1-year follow-up were modeled through two-level hierarchical models with level 1 (the children) and level 2 (the schools). Through this approach we aimed to compare the average change in Hb counts over the two examined periods between different groups of children. Baseline anemia status was also included in the explanatory part of the model to be able to examine rises in Hb levels in anemic and not anemic subjects as earlier recommended.10 We made an effort to control for the fact that by adjusting for baseline anemia the effect of moderate or heavy infection for S. mansoni or hookworm may be underestimated if the type of anemia in the uninfected group is predominantly mild and self-limiting. We therefore also tested the two-way interaction terms of intensity of S. mansoni and of hookworm infections with anemia status, and because none were significant, these were omitted from the model. To test the statistical significance of the fixed effects, Wald tests were used, whereas likelihood ratio tests were performed for the random effects. All of the hierarchical models presented are random intercepts models with multiple independent variables and were obtained using Mlwin (Multilevel Models Project, Institute of Education, London, UK).


RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Because of drop-outs during the second year of the study, baseline and follow-up data concerning the Hb counts were available from 2,788 children, 6–14 years old, from 36 of the 37 schools initially visited at baseline, over the period 2003 and 2004 inclusive. In school Tonya in the Hoima district, Hb counts were measured neither at baseline nor at follow-up so this specific school was not included in this analysis. Table 1Go presents the health indicators of children surveyed during this period. Over the 12 months between examinations, overall prevalence significantly decreased for both S. mansoni and hookworm infections as well as for anemia. For both years of the study the prevalences of severe anemia were negligible and therefore these cases were not examined further here. Similarly, overall point prevalences, at both time-points, for T. trichura and A. lumbricoides were very low. The arithmetic mean intensities for all subjects (negatives and positives) for S. mansoni and hookworm infections decreased significantly 1-year post-praziquantel and albendazole treatment. A significant increase in hemoglobin concentration was also observed during the study period.


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TABLE 1
Health characteristics of children in 2003–2004 successfully followed up for 1 year
 
Table 2Go shows that there were significant differences between the children that were successfully followed up and the drop-outs with reference to their age, sex, home district, and schistosomiasis infection. Children of 6 and 11 years old or above as well as children living in Arua and Mayuge proved most difficult to recruit into the cohort in the second year of the study. The largest recovery cohort failure was observed in children heavily infected with S. mansoni at baseline.


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TABLE 2
Comparison of children successfully followd-up and drop-outs
 
The results of the hierarchical multivariate logistic regression model for the probability of a child being anemic at baseline are presented in Table 3Go. This model included intensities of S. mansoni and hookworm infections and the analysis controlled for age and sex, allowing also for assessment of the extent of between-school variation in anemia prevalence. At follow-up, there were very few children who were heavily infected with hookworm and therefore the convergence of the fitting algorithm in some of the models led us to merge the heavy and moderate hookworm intensities into one category. Moreover, there were very few children that were 9 and 10 years old (only two children were 9 and none were 10 years old) within the cohort with these ages who caused problems to some of the models fits and again we decided to exclude them from all analyses. This was performed in all models presented in this study so that they can be comparable. Also for a similar reason, we do not specifically examine co-infections of schistosomiasis and hookworm, because overall, there were too few co-infected children in our cohort to support model fitting.


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TABLE 3
Adjusted odds ratios from hierarchical multivariate logistic regression model for baseline prevalence of anemia (n = 2,682)
 
Table 3Go shows that children moderately or heavily infected with S. mansoni were marginally significantly more likely to be anemic than those uninfected with S. mansoni. Children moderately or heavily infected with hookworm were significantly more likely to be anemic than those uninfected with hookworm. The school-level variance at the bottom of the same table shows that schools differed significantly in the baseline prevalence of anemia observed. We also tested whether the effects of the intensities of schistosomiasis and hookworm infections varied by age, sex, or state of weight. For this reason we incorporated the relevant two-way interaction terms in the model, and because none of these were significant, these estimates are not presented here.

Results from the hierarchical logistic regression model for the probability of a child being anemic at 1-year follow-up are presented in Table 4Go. Children heavily infected with S. mansoni at follow-up were significantly more likely than uninfected children to be anemic. Age, sex, and moderate or heavy hookworm infections were also significant predictors. Finally, schools varied in the prevalence of anemia observed at follow-up.


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TABLE 4
Adjusted odds ratios from hierarchical multivariate logistic regression model for follow-up prevalence of anemia (n = 2,696)
 
Table 5Go contains the estimates of the three-level hierarchical model for Hb counts before and after praziquantel and albendazole treatment. Normal plots of the different levels residuals appeared fairly linear, which suggested that the assumption of normality and the selection of a linear hierarchical model were reasonable. An overall increase of 0.061 g/dL in the Hb level after chemotherapeutic treatment was not significant (P = 0.115). Children heavily infected with S. mansoni had significantly lower Hb counts (0.322 g/dL; P < 0.001) compared with uninfected children at baseline. Children with moderate or heavy hookworm infection at baseline had significantly lower Hb counts (0.595 g/dL; P < 0.001) than those not infected after controlling for S. mansoni intensity, age, sex, and anemia status. The random effects variance components indicate that much of the variation is between children within a school, but there was also statistically significant variation between schools. The total variance is 1.758, the sum of the three variance components [Var(v0k), Var(u0jk), and Var({varepsilon}0ijk)]. Of the total variability in Hb counts, 0.122/1.758 = 6.94% was situated at the school level, whereas 0.551/1.758 = 31.34% arose between children within a school.


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TABLE 5
Estimates from three-level hierarchical model for hemoglobin counts before and after chemotherapeutic treatment (n = 2,682)
 
Figure 1Go shows 36 level 3 residuals plotted one for each school with the schools ordered according to the rank of their posterior mean. It indicates that most of them have approximately average Hb counts that cannot be distinguished statistically. The school with the lowest intercept residual (at the bottom left) and mean Hb count was Kibiro school in Hoima district. At baseline the S. mansoni and hookworm point prevalences in this school were 94.87% and 10.26%, whereas at follow-up these decreased to 87.18% and 2.56%, respectively. The school with the highest intercept and mean Hb count was Arua Public in the Arua district. The raw data for this school showed that S. mansoni and hookworm prevalence at baseline were 22.86% and 25.71% and decreased to 14.29% and 2.86%, respectively, at follow-up.


Figure 1
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  		    FIGURE 1. Caterpillar plot: 36 level 3 residuals from model presented in Table 5Go (bars represent 95% CIs and the triangles level 3 residuals).

 
Finally, Table 6Go contains the estimates of the two-level hierarchical model for the change of Hb counts between the 2 years of the study. It indicates that most risk groups had a relatively slowed reduction or actual increase in Hb counts after praziquantel and albendazole chemotherapy compared with the reference group (baseline uninfected, non-anemic, ≥ 11 years old). More precisely, children heavily infected with S. mansoni at baseline had a smaller decrease by 0.229 g/dL in their Hb counts in comparison with the uninfected with S. mansoni. Among children found to be anemic at the baseline survey, Hb counts increased significantly by 0.834 g/dL (i.e., 1.240–0.406 g/dL) after treatment.


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TABLE 6
Estimates from two-level hierarchical model for the change of hemoglobin counts (n = 2,682)
 

DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Friedman and others29 recommended that future research aimed to quantify a relationship between schistosomiasis and anemia should include an adequate follow-up period and include individuals with a range of infection intensities. To our knowledge, our study represents the first longitudinal examination into the occurrence of anemia in a cohort of children infected with S. mansoni and hookworm in Uganda using a uniquely detailed large dataset arising from the National Control Schistosomiasis Program within the country. We examined the relationship of S. mansoni and hookworm infection to anemia and Hb levels and evaluated the effectiveness of practical interventions to control or reduce the severity of such anemia.

Helminth infections at a young age may induce, among other factors, pro-inflammatory mediators that are detrimental to protein metabolism, appetite, and erythropoiesis and the WHO therefore recommends the use of anti-schistosome treatment.1 In Uganda, it has been proven that drug distribution in schools is excellent and community-directed treatment is a feasible health approach for mass drug distribution in poor remote communities.30 Our study provides further convincing evidence to show that young children may benefit from deworming in terms of increased Hb and consequently reduced anemia levels. In particular, while our data clearly show there was association between anemia and both schistosomiasis and hookworm infection at baseline, by the follow-up data, the probability of anemia was only associated with heavy S. mansoni and moderate or heavy hookworm infections (Tables 3Go and 4Go).

However, whereas the first hierarchical model of Hb counts (Table 5Go) showed that treatment arrests the drop in Hb, it suggests that without iron replacement, Hb levels probably will not rise. Additionally, the second hierarchical model (Table 6Go) revealed a drop in Hb counts in the comparison group of baseline uninfected, non-anemic, ≥ 11-year-old children. One could speculate that this could reflect, for example, an increased malaria infection rate at follow-up and/or a bad harvest during the second year of this study, perhaps explained from the fact that there were > 1.6 million internally displaced persons in Uganda’s north and east where malnutrition is one of the most pressing health concerns as a result of fighting between government forces and rebels from the Lord’s Resistance Army.31 It is likely that inadequate dietary iron was another factor contributing to this observed decline. These results confirm the findings of Taylor and others32 in South Africa where through a randomized controlled trial provided two different anthelmintic treatment regimens twice at 6-month intervals combined with iron supplementation for 1 year in groups of 428 primary school pupils. These authors observed a significant decrease in Hb levels of pupils receiving triple dose of albendazole and praziquantel only and a significant increase in Hb levels of pupils receiving three doses of these drugs and iron supplementation. Such combined results thereby strengthen the argument of Stoltzfus and others33 that deworming programs should be combined with increased iron intake through supplementation, fortification, or improved diet to reduce the incidence of anemia substantially.

Moreover, data from Beasley and others34 in rural Tanga, Tanzania, and Friis and others35 in western Kenya suggest that children most benefited from anthelmintic treatment in terms of increased Hb levels were those who were anemic at baseline. From our second hierarchical model of Hb counts (Table 6Go), we also found a significant increase in the change of Hb counts and a stronger effect for anemic children compared with non-anemic. This same model also showed a slower reduction in Hb counts for heavily infected children with S. mansoni and moderately or heavily infected children with hookworm compared with uninfected after treatment, which suggests that the effect of anthelmintic treatment on Hb was mediated by reductions in intensities of S.mansoni and hookworm infections.

Ethical reasons as well as the operational reality of the national control program did not permit the inclusion of a control (i.e., untreated) group here. Consequently, the study design did not allow estimation of the absolute impact of treatment only the relative impact in different groups. Therefore, to provide substantial support for the plausibility of the impact of the intervention, the epidemiologic findings from the models presented in this study should be further validated with quantitative predictions arising from mathematical models and this work is underway. The high percentage of drop outs in the group of heavily infected children with S. mansoni (Table 1Go) because of frequent population movements within Uganda, might also add some bias to the epidemiologic findings of this study. Moreover, although malaria is a well-known cause of anemia and Plasmodium falciparum is almost holoendemic in our study population,36 this factor as well as dietary iron intake were not examined, but we highly recommend that this information should be included in future evaluation follow-ups.29 Indeed the variance components of the linear hierarchical models (Tables 5Go and 6Go) have shown that there remains substantial variability that is not explained by the models, and this might well be caused by malaria and iron deficiency not being taken into account here. In addition to these, variables referring to mosquito control at the school/village level were not available, and future studies may benefit from their incorporation. The hierarchical model did, however, show that Kibiro school in Hoima district, with significantly lower mean Hb count compared with the overall mean Hb count, had also very high S. mansoni prevalence, possibly because of its proximity to Lake Albert, the major source of transmission. On the other hand, the school with significantly higher mean Hb count compared with the overall mean Hb count was situated in the northern part of the country, where S. mansoni and hookworm prevalences were moderately low. These results agree with previous work on the distribution of S. mansoni in Uganda, which indicates that highest schistosomiasis prevalences are found close to the eastern shores of Lakes Albert and Victoria, whereas areas of low or zero prevalence are found in the northeast of the country.37

To conclude, our results, from a large scale national control program suggest that S. mansoni and hookworm infections may be related to anemia in specific districts of Uganda and chemotherapy with praziquantel and albendazole may reduce anemia. Anemia is therefore likely to represent a valuable marker for morbidity caused by heavy infection with S. mansoni, provided that other likely causes, such as hookworm, dietary iron intake, and malaria, are taken into consideration.

Received November 11, 2005. Accepted for publication February 15, 2006.

Acknowledgments: We acknowledge the excellent assistance of the Ugandan Vector Control Division field and technical staff and the willing help and collaboration of teachers and children of the schools concerned. We particularly thank H. Namwangye for contribution from Uganda. We also thank Dr. Maria Gloria Basanez and her research group for helpful discussions, Professor Richard Olds for reviewing the manuscript, Dr. Simon Brooker for comments on the text, and Dr. Tom Johnston for advice on statistical issues.

Financial support: The Schistosomiasis Control Initiative (SCI) is generously supported by a grant from the Bill and Melinda Gates Foundation.

* Address correspondence to Artemis Koukounari, Schistosomiasis Control Initiative, Department of Infectious Disease Epidemiology, Imperial College Faculty of Medicine, St. Mary’s Campus, Room G26, Norfolk Place, London W2 1PG, UK, E-mail: artemis.koukounari{at}imperial.ac.uk Back

Authors’ addresses: Artemis Koukounari, Alan Fenwick, Sarah Whawell, and Joanne P. Webster, Schistosomiasis Control Initiative, Department of Infectious Disease Epidemiology, Imperial College Faculty of Medicine, St Mary’s Campus, Norfolk Place, London W2 1PG, UK, E-mails: artemis.koukounari{at}imperial.ac.uk, a.fenwick{at}imperial.ac.uk, joanne.webster{at}imperial.ac.uk. Narcis B Kabatereine, Francis Kazibwe, and Edridah M. Tukahebwa, Vector Control Division, Ministry of Health, Kampala, PO Box 1661, Uganda, E-mails: vcd_sci{at}vcdmoh.go.ug, FKazibwe{at}vcdmoh.go.ug, EdridahT{at}vcdmoh.go.ug. J. Russell Stothard, Department of Zoology, Natural History Museum, Cromwell Road, London SW7 5BD, UK, E-mail: R.Stothard{at}nhm.ac.uk. Chirstl A. Donnelly, Department of Infectious Disease Epidemiology, Imperial College Faculty of Medicine, St. Mary’s Campus, Norfolk Place, London W2 1PG, UK, E-mail: c.donnelly{at}imperial.ac.uk.

Reprint requests: Artemis Koukounari, Schistosomiasis Control Initiative, Department of Infectious Disease Epidemiology, Imperial College Faculty of Medicine, St. Mary’s Campus, Room G26, Norfolk Place, London W2 1PG, UK, E-mail: artemis.koukounari{at}imperial.ac.uk.


REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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C. H. King and M. Dangerfield-Cha
The unacknowledged impact of chronic schistosomiasis
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