The epidemiology and control of urinary schistosomiasis and soil-transmitted helminthiasis in schoolchildren on Unguja Island, Zanzibar

Transactions of the Royal Society of Tropical Medicine and Hygiene (2009) 103, 1031—1044

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The epidemiology and control of urinary schistosomiasis and soil-transmitted helminthiasis in schoolchildren on Unguja Island, Zanzibar J. Russell Stothard a,1, Michael D. French b,c,1, I. Simba Khamis d, María-Gloria Basᘠnez b, David Rollinson a,∗ a

Wolfson Wellcome Biomedical Laboratories, Department of Zoology, Natural History Museum, London SW7 5BD, UK Department of Infectious Disease Epidemiology, Imperial College London, London W2 1PG, UK c Schistosomiasis Control Initiative, Imperial College London, London W2 1PG, UK d Helminth Control Laboratory Unguja, Ministry of Health and Social Welfare, Zanzibar, Tanzania b

Received 22 July 2008; received in revised form 11 March 2009; accepted 11 March 2009 Available online 5 May 2009

KEYWORDS Schistosoma haematobium; Soil-transmitted helminths; Anthelminthics; Chemotherapy; Deworming; Zanzibar; Urinary schistosomiasis

Summary As part of a 4-year control programme beginning in 2003 and entitled Piga Vita Kichocho, around 140 000 school-aged children on Unguja Island, Zanzibar were treated annually with a combination of praziquantel and albendazole. To provide information on the impact of this intervention, a subset of children, originating from 24 sentinel schools, were monitored in 2004, 2005 and 2006 using both parasitological and behavioural questionnaire methods. Overall, prevalence of urinary schistosomiasis fell by 52%, intensity by 55% and gross haematuria by 82%. There was a positive and statistically significant correlation between areas of elevated disease prevalence and areas of predicted high transmission based upon local occurrence of the permissive intermediate snail host. In areas of low transmission, urinary schistosomiasis was greatly reduced, but, by contrast, other intervention strategies are needed to complement and synergise with chemotherapy in high transmission areas. Whereas significant reductions were documented in the prevalence of both Trichuris trichiura and hookworm, prevalence of Ascaris lumbricoides significantly increased over the monitoring period. Through a detailed analysis of named child records, evidence of predisposition to helminth (re)infection and individual bias towards polyparasitism was detected, highlighting the often overlapping distribution of these parasites within the school-aged child. © 2009 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

1. Introduction ∗ Corresponding author. Tel.: +44 20 7942 5181; fax: +44 20 7942 5518. E-mail address: [email protected] (D. Rollinson). 1 These authors contributed equally to this work.

Human infection with schistosomes and soil-transmitted helminths (STHs: comprising the intestinal nematodes) make a significant contribution to the global burden of disease and

0035-9203/$ — see front matter © 2009 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.trstmh.2009.03.024

1032 are estimated to affect over 2 billion people worldwide.1—4 Combined, these diseases may be responsible for the annual loss of 43.5 million disability-adjusted life years (DALYs)5 , with 80—85% of this disease burden occurring in sub-Saharan Africa.6 The major sequelae are anaemia, haematuria, growth stunting and cognitive impairment.7,8 Schistosomiasis and soil-transmitted helminthiases can be easily treated with orally administered praziquantel and albendazole, respectively. These drugs are affordable, efficacious and safe for the large-scale treatment of human populations.9,10 School-aged children tend to be the target of chemotherapy-based control programmes because they carry the heaviest worm and egg burdens. This is due, in part, to their hygiene and behavioural practices, determining higher exposures and rates of acquisition of infection.11 Treatment of children is also likely to be more successful in averting the development of subsequent, more serious disease sequelae because earlier stages of infection-induced pathology may be reversible if treated promptly. School-based deworming projects have been promoted as a cost-effective strategy for the control of infection, even in environments where transmission is deemed to be high.12,13 Parasitological examination of study populations can be used to obtain accurate measures of infection prevalence and intensity but tends to be time-consuming and relatively costly in programmatic contexts. Thus, presumptive treatment of at-risk populations is widely implemented in schistosomiasis and STH control programmes. Along the coast of Tanzania the endemicity of urinary schistosomiasis varies widely14 and at a local level transmission of Schistosoma haematobium can be highly focal. On Unguja Island, Zanzibar, for example, the disease distribution is broadly defined by the distribution of the local permissive intermediate snail host, Bulinus globosus15,16 , and prevalence of infection has been shown to be positively associated with proximity to infected water sources at a very fine-scale level.17 Detailed local knowledge of such heterogeneities inclusive of local human behaviours (assessed with questionnaires pertaining to water-related risk factors, for example) can help to build a better foundation for targeting and evaluating control interventions waged against urinary schistosomiasis.17,18 In this paper we present the salient findings of a monitoring and evaluation programme, inclusive of parasitological and behavioural methodologies, associated with a 4-year control intervention known locally as Piga Vita Kichocho (‘Kick out urinary schistosomiasis’). This programme is targeted (despite its narrower title) towards reducing both urinary schistosomiasis and soil-transmitted helminthiases in primary school children on Unguja Island, Zanzibar.

2. Materials and methods 2.1. Study area and selection of schools, classes and children As part of Piga Vita Kichocho, school-age children have been treated with praziquantel and albendazole concurrently each year since its inception in 2003. Treatments were administered in schools with the assistance of teachers and health workers and reached around 140 000 children. The

J.R. Stothard et al.

Figure 1 Sketch map of the three coastal islands of Tanzania: Pemba, Unguja and Mafia [insert] and detailed map of the 24 sentinel schools on Unguja Island with known water contact sites harbouring Bulinus globosus (crosses) and B. nasutus (diamonds)53 . The schools that are situated in high transmission locations are denoted by a boxed square.

programme is run jointly by the Natural History Museum, London (NHM) and the Ministry of Health & Social Welfare, Zanzibar, and receives support from the Schistosomiasis Control Initiative, UK. Although school attendance rates are high on Unguja (87%), efforts were also made to include nonenrolled children in the treatment programme, as they can often harbour the heaviest infections and contribute most to transmission.19 To monitor the impact of the intervention, a subset of 24 spatially geo-referenced sentinel schools across the island were selected in order to provide a representative crosssection of schoolchildren. Criteria for selection as sentinel schools included a good geographical spread and an appropriate representation of endemicity levels; nine in high transmission areas and 15 in low transmission areas (see section 2.2 below, Table 1, Figure 1). The classes tested each year were chosen in order to maximize the numbers of children followed-up longitudinally, with a new cohort of Standard I children (the youngest class) added each year (Table 2). A subset of children (2004, n = 2002; 2005, n = 3278; 2006, n = 3993) was examined. The data obtained from this survey constitute chiefly a cross-sectional, annual representation of infection and morbidity status at the time of examination by parasitological, urological and questionnaire methods (see below). Monitor-

Piga Vita Kichocho on Unguja Island Table 1 No.

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

1033

GPS coordinates of 24 sentinel schools monitored during Piga Vita Kichochoa and treatment details for 2004 to 2006

School name

Nungwi Mwanda Pwani Mchangani Chaani Kinyasini Mahonda Kitope Skul Mchangani Mwenge Uzini Kiboje Mwera Fujoni Mtopepo Regeza Mwendo Rahaleo Nyerere Jang’ombe B Fuoni Kombeni Jambiani Muyuni Kizimkazi Mkunguni Mtende

High/low transmission zone

Low Low Low High High High High High High Low High High Low Low High Low Low Low Low Low Low Low Low Low

GPS co-ordinates

Date for each round of treatment

Latitude

2004

2005

2006

21 11 27 09 21 27 11 17 27 17 24 24 11 17 27 21 17 22 01 01 07 07 14 14

07 March 15 March 10 March 07 March 10 March 15 March 18 March 23 March 11 April 23 March 29 March 29 March 18 March No treatment 11 April 27 April No treatment 27 April 18 April 18 April 08 April 08 April 04 April 04 April

19 27 24 24 24 24 02 02 22 08 11 11 02 10 02 29 01 29 25 25 18 18 15 15

S S S S S S S S S S S S S S S S S S S S S S S S

5◦ 5◦ 5◦ 5◦ 5◦ 5◦ 6◦ 6◦ 6◦ 6◦ 6◦ 6◦ 6◦ 6◦ 6◦ 6◦ 6◦ 6◦ 6◦ 6◦ 6◦ 6◦ 6◦ 6◦

43.732 55.156 55.228 55.799 58.216 59.562 01.314 02.623 03.521 04.318 04.870 08.629 09.470 08.789 08.965 09.878 10.105 10.510 12.830 15.534 19.000 22.708 26.270 27.032

Longitude E E E E E E E E E E E E E E E E E E E E E E E E

39◦ 39◦ 39◦ 39◦ 39◦ 39◦ 39◦ 39◦ 39◦ 39◦ 39◦ 39◦ 39◦ 39◦ 39◦ 39◦ 39◦ 39◦ 39◦ 39◦ 39◦ 39◦ 39◦ 39◦

17.577 14.145 21.358 17.972 18.494 15.225 15.452 20.076 19.249 19.771 18.425 16.334 12.344 13.282 15.441 12.184 10.498 12.345 15.902 15.653 32.600 27.849 28.000 31.861

April May April March April April March May May May May May May June May June June June June June June June June June

April April April April April April May May May May May May May June May May June May May May May May June May

a

Each school is denoted to lie within either putative ‘high’ or ‘low’ transmission areas, which is based primarily upon the proximity to habitats harbouring Bulinus globosus.53 NA denotes not available.

Table 2

Sampling protocol for each year of treatment

Year

Standards chosen for samplinga

2004: baseline 2005: follow-up Year 1 2006: follow-up Year 2

I, IV I, II, V I, II, III, VI

a

‘Standards’ correspond to the schooling year. The protocol design was chosen so that classes could be followed throughout the study.

ing was carried out before treatment (usually 1—2 months before) in order to take into account any reinfection, to include younger children entering the school system and to identify children who may have missed treatment at school. Written informed consent to all anticipated medical interventions, including parasitological surveys, was given by parents and/or legal guardians upon enrolment of their children at school. Information concerning the study was provided by members of the Helminth Control Team to village leaders (shehias), headmasters, teachers and children at school.

2.2. Climate, rainfall patterns and transmission areas Unguja is the larger of the two main islands that make up Zanzibar. It is situated in the Indian Ocean off the

coast of mainland Tanzania, with approximate coordinates of 5◦ 42 S to 6◦ 29 S and 39◦ 11 E to 39◦ 35 E. Rainfall patterns are marked by two distinct rainy seasons, related to the monsoons. The heavy rains (accounting for 40% of annual rainfall) occur during the months of March to May, with a lesser rainy season (20% of annual rainfall) from October to December (Figure 2A). Given its tropical location, temperature and humidity are reasonably high and constant throughout the year (Figure 2B). In order to minimize the impact of any seasonal effects on parasite transmission, as far as possible, surveys were carried out at the same time each year, during the heavy rainfall season (Table 1). The distributions of the snail intermediate host B. globosus and of the infection-refractive B. nasutus have been mapped on the island previously.16 Schools situated within areas of B. globosus distribution were classified as potentially high transmission areas and other schools were classified as being in low transmission areas. Figure 1 shows the location of the 24 sentinel schools in either ‘high’ or ‘low’ transmission areas, respectively.

2.3. Parasitological and urological samples Each child presented a mid-morning urine sample, which was graded visually by pupil, school teacher and laboratory technician (from the Helminth Control Laboratory Unguja) for presence of gross haematuria (visible blood in urine) on a scale of 1—6; 1 represented normal urine and 6 represented dark red blood in urine, with a grading of 4—6

1034

J.R. Stothard et al. the child played in freshwater streams, worked in rice paddies and washed clothes. An earlier study17 had conducted an analysis of water contact at one of the sentinel schools (Chaani) using self-reported questionnaires to assess water-contact behaviour. These authors found that playing, swimming and washing in infected water sources, as well as distance from an infected water source to the respective village, were good predictors of S. haematobium infection. The possibility of water contamination was assessed by the prevalence of positive answers to the question of whether the child urinated in water. The questionnaire was prepared in Kiswahili (the local language on Unguja), and its design can be found at http:// www.nhm.ac.uk/hosted sites/schisto/jrs/unguja.html.

2.5. Statistical analysis

Figure 2 Climatic data for Unguja Island. (A) Average monthly rainfall from January 1999 to June 2006, calculated from data presented by54 . (B) Monthly temperature (Temp) and relative humidity (rH) from March 1996 to July 1997, summarized from data presented by55 .

indicating gross haematuria. Urine was then tested using Hemastix (Bayer, Fernwald, Germany) dipstick reagents for semi-quantitative assessment of microhaematuria.20 A 10 ml sample of urine was syringe-filtered through a 12 ␮m polycarbonate filter (Millipore, Livingston, UK) for detection of S. haematobium eggs. Eggs were counted per 10 ml urine sample; any samples that contained more than 50 eggs/10 ml were categorized as 50+ (indicating heavy infection, see below). Each child presented a stool sample, which was analysed using the Kato—Katz thick smear technique21 , followed by microscopic analysis for presence, identification and enumeration of eggs of STHs [Ascaris lumbricoides (roundworm); Trichuris trichiura (whipworm); and Necator americanus/Ancylostoma duodenale (hookworm)] per gram of faeces (epg).

2.4. Questionnaire At the time of urine collection, each child was interviewed individually by the school teacher with a standard questionnaire to record socio-demographic information (e.g. age, sex, school, grade); disease symptoms (e.g. headaches, abdominal pain); and potential helminth infection risk factors, with particular emphasis on water-contact behaviour. An overall water contact score was calculated by aggregating the binary responses to the questions of whether

Despite efforts to recruit a large number of children into the study, there were insufficient children identified at all time points for a valid longitudinal analysis across the 3 years. Therefore, most analyses were conducted using a cross-sectional cohort of children at each time point. However, the dataset permitted two separate sub-analyses: one for those individuals followed up between Year 1 and Year 2, and another for those individuals followed up between Year 2 and Year 3. Data were collected as paper records in Zanzibar and subsequently coded and entered into Microsoft Excel 2003 (Microsoft Corp., Redmond, WA, USA) and analysed using R version 2.3.1 (http://www.r-project.org/) at the NHM and Imperial College London. 2.5.1. Descriptive statistics and measures of central tendency When data were not normally distributed, logtransformations [log(x+1)] were used to stabilize the variance, and in order to conduct appropriate parametric tests. Infection prevalence is reported with exact 95% CI22 ; infection intensity is reported as Williams’ geometric means23 with asymmetric 95% confidence intervals (CI); comparison of means was done via z-tests of the normal distribution for large sample sizes on the log-transformed (normalized) variables.24 Prevalence values before the introduction of ‘Piga Vita Kichocho’ and 3 years later were compared by z-tests on the difference between two proportions. The proportional reduction over treatments of infection and disease prevalence and intensity was estimated as the absolute value of the ratio of the difference between the final and initial values to the initial value, expressed as a percentage. Infection predisposition was analysed by one-way ANOVA.24 2.5.2. Logistic regression Univariate and multivariate logistic regression models were constructed to explore the relationship between infection or morbidity prevalence and the variables that were measured at individual and school levels. This was done using the 2004 baseline data before treatment to avoid any influence of the monitoring project, such as increased awareness about water contact and the disease. Random effects logistic regression models were constructed to control for the effects of clustering at school level. Separate models were

Piga Vita Kichocho on Unguja Island

Figure 3 Schistosoma haematobium infection trends in monitored schoolchildren, boys and girls, in the 24 sentinel schools on Unguja Island over 3 years of Piga Vita Kichocho by (A) prevalence (% infected) and (B) intensity [Williams’ geometric mean (GM) no. eggs/10 ml of urine]. Error bars are 95% CI.

constructed for any infection and heavy infection of schistosomiasis and STHs according to WHO guidelines, which define heavy infection with urinary schistosomiasis as that in which the individual presents ≥50 eggs/10 ml urine.21 Owing to low baseline levels of STH infection, our ‘heavy’ category combined both WHO ‘heavy’ and ‘medium’ categories to yield more datapoints and make comparisons valid yielding ≥5000 epg for A. lumbricoides, ≥1000 epg for T. trichiura and ≥2000 epg for hookworms.9 Interactions between variables were included at first and removed if they proved to be non-significant. The most parsimonious yet adequate models that best fitted the data were constructed using stepwise analysis and chosen by comparing their Akaike Information Criterion (AIC) scores.25 A significance level of ␣ = 0.05 was used throughout.

3. Results 3.1. Urinary schistosomiasis The overall prevalence of S. haematobium infection fell by 52% between 2004 and 2006 [from 13.2% (95% CI 11.7—14.7) to 6.4% (95% CI 5.4—7.4); z = 7.68, P < 0.001; Figure 3A] with a corresponding drop in overall intensity of 55% (0.51 to 0.23 eggs/10 ml urine; z = 9.85, P < 0.001; Figure 3B). However, there was variability between schools in their prevalence and intensity trends over the monitoring period (data not shown) with most schools exhibiting a decreasing trend but

1035

Figure 4 Comparison in reductions of Schistosoma haematobium infection between high and low transmission areas on Unguja Island over 3 years of Piga Vita Kichocho by (A) prevalence (% infected) and (B) intensity [Williams’ geometric mean (GM) no. eggs/10 ml of urine]. Error bars are 95% CI.

some schools displaying stable values and some even displaying a rise. For example, infection prevalence in Mwera School more than doubled in the period between 2004 and 2006, increasing from 17.1% (95% CI 14.0—20.1) to 37.0% (95% CI 28.9—45.2; z = 3.14, P = 0.002). Boys consistently showed higher infection prevalence and intensity than girls, although reductions were seen in both sexes (Figure 3). Reductions of infection prevalence and intensity were seen both in schools situated within putative high and low transmission zones (Figure 4). In those schools of the high transmission areas, the prevalence of S. haematobium decreased by 50% [from 31.6% (95% CI 27.8—35.3) to 15.7% (95% CI 13.2—18.1); z = 7.11, P < 0.001] and in those of the low transmission areas by 80% [from 5.9% (95% CI 4.6—7.1) to 1.2% (95% CI 0.6—1.7); z = 6.77, P < 0.001]. Correspondingly, infection intensity fell by 59% in schools within high transmission areas [from 1.64 (95% CI 1.33—1.99) to 0.67 (95% CI 0.54—0.81) eggs/10 ml urine; z = 12.73, P < 0.001], and by 86% [from 0.21 (95% CI 0.16—0.26) to 0.03 (95% CI 0.02—0.05) eggs/10 ml urine; z = 7.53, P < 0.001] in those within low transmission areas. The prevalence of gross haematuria (visible blood in urine) fell by 82% [from 3.9% (95% CI 3.0—4.7) to 0.7% (95% CI 0.4—1.1); z = 7.13, P < 0.001; Figure 5], and the prevalence of total haematuria (visible and micro-haematuria) fell by 53% [from 15.4% (95% CI 13.8—16.9) to 7.3% (95% CI 6.3—8.3); z = 8.50, P < 0.001; Figure 5]. Girls and boys displayed similar patterns of reduction, although boys consistently suffered higher haematuria values than girls, which probably reflects their higher S. haematobium infection patterns (Figure 3).

1036

J.R. Stothard et al. The same relationship can be seen when the dataset is split into schools situated within areas of high and low transmission. Gross haematuria fell by 79% [from 8.0% (95% CI 5.8—10.3) to 1.7% (95% CI 0.8—2.5); z = 5.80, P < 0.001] and by 96% [from 2.3% (95% CI 1.5—3.1) to 0.1% (95% CI 0.0—0.3); z = 5.22, P < 0.001] in schools located in high and low transmission areas, respectively. Total haematuria fell by 55% [from 36.8% (95% CI 32.8—40.6) to 16.4% (95% CI 13.6—18.5); z = 8.92, P < 0.001] and by 62% [from 6.8% (95% CI 5.4—8.1) to 2.6% (95% CI 1.8—3.4); z = 5.27, P < 0.001] in areas of high and low transmission, respectively.

3.2. Risk factors associated with urinary schistosomiasis Figure 5 Decline of gross haematuria as measured by visual inspection of the urine by a laboratory technician (solid lines), and total haematuria, inclusive of gross- and micro-haematuria, (dashed lines) over 3 years of Piga Vita Kichocho. Error bars are 95% CI.

Table 3

There was a reduction in water contact (as measured by combining positive answers to the questions of playing, working and washing in water bodies) of 46% between 2004 and 2006 [from 38.4% (95% CI 36.3—40.1) to 20.9% (95% CI 17.6—24.2); z = 12.76, P < 0.001; Figure 6], albeit with considerable heterogeneity between schools. For example,

Results of multivariate logistic regression to calculate the 2004 odds ratios of infection with Schistosoma haematobiuma

Factor

Variableb

Any infection Estimate (95% CI)

Sex Age (years)

STH infections

Area Water contact score Feeling unwell Headaches Abdominal pain Access to fresh water Urinate in streams Ever taken schistosomiasis medication No. treatment rounds a

Heavy infection (≥50 eggs/10 ml urine) P-value Estimate (95% CI)

Femalesc Males 1.195 (0.894—1.597) 0.229 Age group <10c Age group 10—12 2.058 (1.437—2.945) <0.001 Age group >12 2.644 (1.638—4.265) <0.001 A. lumbricoides log (epg+1) 1.012 (0.930—1.100) 0.784 T. trichiura log (epg+1) 1.059 (0.973—1.151) 0.185 Hookworm log (epg+1) 1.151 (1.052—1.258) 0.002 Low transmissionc High transmission 10.033 (3.034—33.17) 0.001 Per 10% rise 1.075 (0.988—1.170) 0.092 Noc Yes 1.125 (0.626—2.017) 0.693 Noc Yes 1.094 (0.760—1.574) 0.629 Noc Yes 1.533 (1.021—2.302) 0.039 Noc Yes 2.042 (0.584—7.132) 0.264 Noc Yes 1.876 (1.246—2.823) 0.003 Noc

P-value

1.660 (1.171—2.350)

0.004

1.275 1.766 0.988 1.140 0.936

(0.830—1.959) (1.017—3.065) (0.894—1.092) (1.036—1.254) (0.829—1.057)

0.267 0.043 0.819 0.007 0.289

7.497 (1.477—38.04) 1.137 (1.005—1.284)

0.024 0.041

1.811 (0.992—3.304)

0.053

1.003 (0.626—1.605)

0.991

1.515 (0.895—2.563)

0.122

1.788 (0.335—9.527)

0.496

4.729 (2.916—7.667) <0.001

Yes

2.161 (1.081—4.321)

0.029

1.227 (0.550—2.732)

0.617

Per round increase

0.704 (0.431—1.150)

0.161

0.809 (0.159—4.107)

0.417

All analyses (for the 2004 data) correspond to mixed-effects models controlling for random effects of schools. Explanatory variables: Log (egg count+1) = increase in one unit of log (epg+1) or log (eggs+1/10 ml urine); all log transformations use natural logarithms; Water contact score = 10 percentage point rise in water contact score, as detailed in the methods; Headaches = Have you suffered from headaches in the past year? Abdominal pain = Have you suffered from abdominal pain in the past year? Ever taken medication = Ever taken medication for schistosomiasis? No. treatment rounds = No. of times pupil has ever taken medicine for schistosomiasis. c Denotes the reference group. b

Piga Vita Kichocho on Unguja Island

1037 schistosomiasis medicine before were twice as likely to be infected as those reporting no prior treatment (OR = 2.16, P = 0.029). No interaction terms were found that were significant or that improved the model fit at bivariate level.

3.3. Soil-transmitted helminthiases

Figure 6 Changing dynamics of overall water contact scores and water contamination as assessed by school questionnaires in the 24 sentinel schools on Unguja Island over 3 years of Piga Vita Kichocho. Water contact scores are expressed as percentages of a maximum score of 1 representing positive answers to each of three water contact questions (i.e. playing, working, and washing in water bodies, see Materials and methods). Water contamination is assessed by the prevalence of positive answers to the question of whether the child urinated in water. Error bars are 95% CI.

Kinyasini School showed a 50% increase in water contact [from 45.7% (95% CI 35.9—55.4) to 68.7% (95% CI 58.7—78.6); z = 3.12, P = 0.002]. Water contamination (measured as the proportion of positive answers to the question of whether children urinate in water) decreased by 60.3% [from 14.8% (95% CI 13.3—16.4) to 5.7% (95% CI 4.9—6.5); z = 10.91, P < 0.001; Figure 6), again with considerable inter-school heterogeneity (data not shown). The sex of the children is a strong risk factor for heavy infection, with boys at a higher risk than girls [odds ratio (OR) = 1.66, P = 0.004; Table 3), even after controlling for behavioural factors, although the relationship did not reach statistical significance for all infections (OR = 1.20, P = 0.229). There were significant increases in the odds ratio of infection with increasing age, with the oldest age group being typically twice as likely to harbour all and heavy infection (OR = 2.06, P < 0.001 and OR = 2.64, P < 0.001, respectively). Each additional increase in one unit of log (epg) of hookworm intensity had a significant increase on the risk of schistosome infection (OR = 1.15, P = 0.002), but not heavy infection. Increases in T. trichiura intensity had a significant effect on heavy schistosome infections (OR = 1.14, P = 0.007), whereas equivalent increases in A. lumbricoides did not alter the odds of schistosomiasis infection (OR = 1.01, P = 0.784) and heavy infection (OR = 0.99, P = 0.819). Location of schools in high transmission areas significantly and strongly increases the odds of infection and heavy infection (OR = 10.03, P < 0.001 and OR = 7.50, P = 0.024, respectively). Each 10% increase in water contact score had a borderline significant association with infection (OR = 1.08, P = 0.092) and heavy infection (OR = 1.14, P = 0.041). Urinating in streams was strongly and significantly associated with the risk of schistosomiasis (OR = 1.88, P = 0.003), and almost a 5-fold increase for heavy infection (OR = 4.73, P < 0.001). Those children who reported having taken anti-

The prevalence of A. lumbricoides infection rose by 23% over the course of the programme [from 9.2% (95% CI 8.0—10.5) to 11.3% (95% CI 10.0—12.5); z = 2.20, P = 0.027; Figure 7) and intensity rose by 33% [from 0.9 epg (95% CI 0.7—1.0) to 1.2 epg (95% CI 1.0—1.5); z = 5.85, P < 0.001), although both were at a low value by the time the programme started. By contrast, there were significant reductions in the prevalence of T. trichiura [by 29%; from 17.7% (95% CI 16.0—19.4) to 12.5% (95% CI 11.2—13.9); z = 4.78, P < 0.001] and of hookworm infection [by 44%; from 7.7% (95% CI 6.6—8.9) to 4.3% (95% CI 3.5—5.1); z = 4.87, P < 0.001], and in the intensity of infection {with T. trichiura decreasing by 47% [from 1.5 epg (95% CI 1.3—1.7) to 0.8 epg (95% CI 0.7—0.9); z = 11.50, P < 0.001] and hookworm by 40% [from 0.5 epg (95% CI 0.4—0.7) to 0.3 epg (95% CI 0.23—0.33); z = 15.58, P < 0.001]}. Historical information on the secular trends of STH prevalence and intensity in school-aged children was obtained from unpublished records by the Ministry of Health and Social Welfare, Zanzibar. These data were gathered from schoolchildren in the same areas, and in the majority of cases from the same schools included in the current study. Analyses of these data revealed that there have been marked decreases in the prevalence and intensity for each of the three intestinal nematodiases from 1994 to 2004 (Figure 7), most probably as a result of other control initiatives. At the 1994 baseline, T. trichiura and hookworm infections were nearly ubiquitous, while A. lumbricoides infected over half of the population.

3.4. Risk factors associated with STHs 3.4.1. Ascariasis After controlling for other variables, boys were almost three times as likely to be heavily infected as girls (OR = 2.94, P = 0.002; Table 4). Infection with A. lumbricoides was positively and significantly associated with that by T. trichiura [OR = 1.63, P < 0.001 for each unit increase in the log(epg+1)] and that by hookworm (OR = 1.10, P = 0.021), the associations also holding for heavy infections (OR = 1.72, P < 0.001 and OR = 1.16, P = 0.020 respectively). Heavy A. lumbricoides infection was positively and significantly associated with intensity of S. haematobium infection (OR = 1.941, P < 0.001). Water contact was positively and significantly associated with A. lumbricoides infection (OR = 1.13, P = 0.003). Feeling unwell was positively associated with A. lumbricoides infection (OR = 2.26, P = 0.019) and heavy infection (OR = 8.95, P = 0.049), although the latter was only borderline significant. Surprisingly, abdominal pain was negatively and significantly associated with heavy ascariasis (OR = 0.48, P < 0.001). Having access to fresh water significantly reduced the odds of infection (OR = 0.30, P = 0.008).

Variable (baseline)a

A. lumbricoides infection

Sex (females) Age (years) (age group <10) Helminth infections (continuous)

T. trichiura infection

Water contact score Feeling unwell (No) Headache (No) Abdominal pain (No) Access to fresh water (No) Urinate in streams (No) Sex (females) Age (years) (age group <10) Helminth infections (continuous)

Hookworm infection

Water contact score Feeling unwell (No) Headache (No) Abdominal pain (No) Access to fresh water (No) Urinate in streams (No) Sex (females) Age (years) (age group <10) Helminth infections (continuous)

Males Age group 10—12 Age group >12 S. haematobium in log(egg count+1) T. trichiura in log(egg count+1) Hookworm in log(egg count+1) Per 10% rise Yes Yes Yes Yes Yes Males Age group 10—12 Age group >12 S. haematobium in log(egg count+1) A. lumbricoides in log(egg count+1) Hookworm in log(egg count+1) Per 10% rise Yes Yes Yes Yes Yes Males Age group 10—12 Age group >12 S. haematobium in log(egg count+1) A. lumbricoides in log(egg count+1) T. trichiura in log(egg count+1) Per 10% rise Yes Yes Yes Yes Yes

Heavy infectionb

Any infection Estimate (95% CI)

P-value

Estimate (95% CI)

P-value

1.272 0.866 0.799 1.016 1.627 1.101 1.128 2.262 0.935 0.811 0.303 1.042 0.891 1.070 0.750 1.072 1.445 1.465 0.970 0.900 0.907 0.983 0.733 1.434 1.239 0.794 0.623 1.106 1.065 1.559 1.049 0.815 1.103 0.876 1.540 0.894

0.212 0.503 0.522 0.859 <0.001 0.021 0.003 0.019 0.777 0.386 0.008 0.893 0.403 0.662 0.287 0.307 <0.001 <0.001 0.315 0.682 0.584 0.929 0.445 0.166 0.247 0.262 0.190 0.217 0.063 <0.001 0.214 0.536 0.682 0.587 0.430 0.706

2.944 0.628 — 1.941 1.718 1.160 0.928 8.946 0.159 0.360 — 0.550 0.312 0.636 — 0.655 1.464 1.454 0.973 0.187 0.315 2.686 0.062 1.687 0.355 0.082 — 2.585 1.113 1.297 1.081 0.069 — 0.342 0.073 —

0.002 0.191 — <0.001 <0.001 0.023 0.442 0.049 <0.001 0.011 — 0.318 0.001 0.153 — 0.019 <0.001 <0.001 0.675 0.033 0.008 0.021 <0.001 0.391 <0.001 <0.001 — <0.001 0.100 <0.001 0.131 <0.001 — 0.011 <0.001 —

(0.871—1.857) (0.567—1.320) (0.403—1.585) (0.856—1.204) (1.510—1.752) (1.014—1.193) (1.042—1.220) (1.145—4.468) (0.586—1.489) (0.504—1.303) (0.125—0.730) (0.570—1.903) (0.678—1.168) (0.790—1.448) (0.440—1.274) (0.938—1.224) (1.358—1.535) (1.362—1.575) (0.913—1.029) (0.542—1.491) (0.639—1.286) (0.678—1.425) (0.330—1.625) (0.861—2.385) (0.862—1.779) (0.531—1.187) (0.307—1.264) (0.942—1.297) (0.996—1.138) (1.449—1.676) (0.973—1.130) (0.426—1.558) (0.691—1.759) (0.541—1.414) (0.527—4.492) (0.500—1.597)

(1.511—5.732) (0.310—1.272) (1.337—2.816) (1.440—2.049) (1.011—1.330) (0.762—1.128) (1.015—78.79) (0.061—0.406) (0.164—0.789) (0.169—1.781) (0.160—0.607) (0.339—1.191) (0.460—0.931) (1.327—1.614) (1.318—1.603) (0.848—1.116) (0.040—0.864) (0.135—0.731) (1.156—6.239) (0.021—0.175) (0.510—5.577) (0.201—0.627) (0.025—0.261) (1.964—3.401) (0.970—1.276) (1.176—1.430) (0.980—1.192) (0.015—0.301) (0.150—0.779) (0.028—0.186)

a Explanatory variables: Log (egg count+1) = increase in one unit of log (epg+1) or log [(eggs/10 ml urine)+1]; Water contact score = 10 percentage point rise in water contact score, as detailed in the methods; Headaches = Have you suffered from headaches in the past year? Abdominal pain = Have you suffered from abdominal pain in the past year?. b Heavy infection is a combination of WHO heavy and moderate categories9 , i.e. ≥5000 epg for A. lumbricoides, ≥1000 epg for T. trichiura, and ≥2000 epg for hookworm.

J.R. Stothard et al.

Water contact score Feeling unwell (No) Headache (No) Abdominal pain (No) Access to fresh water (No) Urinate in streams (No)

Factora

1038

Table 4 Multivariate logistic regression odds ratios for Ascaris lumbricoides, Trichuris trichiura and hookworm infection in 2006 data with regard to reference category of explanatory variable

Piga Vita Kichocho on Unguja Island

1039

Table 5 Reinfection intensities at follow-up for children found infected at previous survey compared to levels of children not infected at previous surveya Helminth

S. haematobium A. lumbricoides T. trichiura Hookworm a

Year

2005 2006 2005 2006 2005 2006 2005 2006

Infection intensity at follow-up (epg or eggs/10 ml urine) Those infected at previous survey (N)

Those not infected at previous survey (N)

2.33 0.47 7.61 13.96 1.17 2.50 1.06 0.27

0.22 0.13 0.73 0.47 0.67 0.54 0.33 0.19

(85) (85) (80) (95) (126) (124) (51) (52)

(610) (798) (615) (788) (569) (759) (644) (831)

Relative risk (infected/not infected)

ANOVA F-value

P-value

10.61 3.53 10.43 29.40 1.76 4.65 3.22 1.43

61.465 4.0229 23.571 51.154 0.0277 28.194 0.0964 0.1626

<0.001 0.045 <0.001 <0.001 0.868 <0.001 0.756 0.687

The two follow-up periods: 2005 compared to previous survey in 2004; 2006 compared to previous survey in 2005.

3.4.2. Trichuriasis Infections showed a significant association with the sex of the children, this time with boys less likely to be heavily infected (OR = 0.34, P = 0.001; Table 4). Heavy T. trichiura infection showed a statistically significant and positive association with that of other STH species (OR = 1.46, P < 0.001 for Ascaris, and OR = 1.45, P < 0.001 for hookworm), but a negative association with S. haematobium (OR = 0.66, P = 0.019). Heavy infection was positively associated with abdominal pain (OR = 2.69, P = 0.021), and negatively associated with feeling unwell (OR = 0.19, P = 0.033), having a headache (OR = 0.32, P = 0.008), and having access to fresh water (OR = 0.06, P < 0.001). 3.4.3. Hookworm infection Boys were significantly less likely to be heavily infected with hookworms than girls (OR = 0.36, P < 0.001; Table 4). Trichuris trichiura infection was positively and significantly associated with all and heavy hookworm infection (OR = 1.56, P < 0.001 and OR = 1.30, P < 0.001 respectively), and heavy hookworm infection was associated with S. haematobium infection (OR = 2.59, P < 0.001). Heavy hookworm infection was negatively and significantly associated with abdominal pain (OR = 0.34, P = 0.011). Access to clean, fresh water had a significant protective effect on heavy hookworm infection (OR = 0.07, P < 0.001), while feeling unwell was negatively and significantly associated with it (OR = 0.07, P < 0.001). No interaction terms that improved the fit of the model were found for any species of STH.

3.5. Reinfection trends and patterns In total, 1578 children were successfully followed-up across two time points (2004—2005 and 2005—2006) (girls = 919, boys = 659, median age at baseline = 11 years). Analysis of these cohorts permitted a direct measure of parasitological markers in those individuals treated, as well as any possible predisposition to infection. Reductions in infection intensity and prevalence in these two longitudinal subcohorts reflected those seen in the cross-sectional cohorts (Figure 8). Intensity of infection fell from 0.41 (95% CI

0.31—0.51) to 0.38 (95% CI 0.28—0.49) eggs/10 ml urine (z = 0.48, P = 0.629) between 2004 and 2005 and from 0.37 (95% CI 0.28—0.46) to 0.16 (95% CI 0.11—0.21) eggs/10 ml urine (z = 5.11, P < 0.001) between 2005 and 2006. Correspondingly, prevalence fell from 12.23% (95% CI 9.79—14.67) to 10.07% (95% CI 7.83—12.31; z = 1.37, P = 0.171) between 2004 and 2005 and from 9.63% (95% CI 7.43—11.82) to 5.10% (95% CI 3.46—6.73; z = 3.46, P < 0.001). These sub-cohorts also allowed testing of whether those children who were infected with helminths at the first survey had heavier infections at the second than those who had been not infected previously. Children who were infected at the 2004—2005 survey had significantly higher intensities of S. haematobium and A. lumbricoides infections than children who were originally not infected. Trichuris trichiura showed higher intensities in previously infected children than previously uninfected children in both years, but this only reached statistical significance in the second follow-up period. The intensity of hookworm infection was higher in previously infected children than previously uninfected children, but this failed to reach statistical significance (Table 5).

4. Discussion From an overall perspective, the Piga Vita Kichocho programme has significantly reduced prevalence and intensity of S. haematobium infections over the course of its first 3 years of implementation, as both of these fell by more than 50%. Worm burden is considered to be an important factor associated with the development of morbidity,26,27 so it is reassuring to note that the prevalence of gross and total haematuria also fell substantially and significantly (by 82 and 53%, respectively) over the course of the programme, presumably easing the disease burden of those individuals treated. Such a beneficial impact has been previously observed in chemotherapy-based programmes on neighbouring Pemba Island.28 Gross haematuria is a good indicator of morbidity29 so reductions in haematuria will lead not only to short-term decreases in morbidity, but also to reductions in the incidence of the more serious sequelae of urinary schistosomiasis.8 As would be expected, boys have higher

1040

Figure 7 Change in soil-transmitted helminth infections, Ascaris lumbricoides, Trichuris trichiura and hookworm, across the 24 monitored schools on Unguja Island during 3 years of Piga Vita Kichocho. (A) Prevalence from 1994 to 2006. (B) Prevalence from 2004 to 2006. (C) Intensity (geometric mean no. eggs/gram of faeces), from 2004 to 2006. The 1994 data are from the Ministry of Health and Social Welfare, Zanzibar and cover a total of 39 primary schools with approximately 40 children per school examined. Note that in 2000—2005 the Global Programme for Elimination of Lymphatic Filariasis conducted annual mass drug administration with ivermectin + albendazole for lymphatic filariasis, which is likely to have impacted upon general STH levels. Error bars are 95% CI.

J.R. Stothard et al. alone is sufficient to contain disease. However, in high transmission areas reduction of infections with chemotherapy alone is much harder to achieve, and additional synergistic intervention strategies are needed to bolster a lasting impact of chemotherapy. Indeed, there are marked differences in infection and disease markers between high and low transmission areas, as predicted by the distribution of the local permissive intermediate host,16,53 and better knowledge of the distribution of this snail could potentially help to fine-tune areas for future focusing of intervention efforts especially as snail numbers fluctuate through time. For example, significant variation in infection markers was seen between schools, with some, e.g. Mwera, registering a rise in prevalence of schistosomiasis that can be explained in part by local environmental determinants. Mwera School is situated near a shallow-sided valley with the Mwera River running through it, and it is regularly flooded. During dryer periods and seasons, reduction of the river leads to the creation of many surface ponds, which offer places for children to play in, in a similar manner to that witnessed by Rudge et al.17 in the stream system surrounding Chaani School (see Table 1 and Figure 1). Thus it can be surmised that the distribution and ecology of the intermediate host and the geography and climate of the location, as also seen in Dar es Salaam,30 play a crucial role in affecting local transmission, which may counter the impact of chemotherapy. Water contact and water contamination rates decreased significantly over the monitoring period, which would have contributed to the reductions in schistosomiasis observed. At the same time, however, this might also reflect the lower number of ephemeral ponds in which children might play, within which in certain instances (e.g. Mwera) transmission foci might even concentrate. In addition to chemotherapy, Piga Vita Kichoho has also implemented a health education component through utilization of the comic strip booklet Juma na Kichocho across intervention schools.31 If the change in water contact has been brought about by behavioural change, it is possible that further reductions in these rates will lead to further improvements if children are taught, and able to understand, the risks and consequences

rates of haematuria than girls, reflecting their higher intensities of infection and water contact rates.17

4.1. Transmission zones In low transmission areas, the levels of both prevalence and intensity of infection have nearly reached zero, which suggests that reinfection levels are low and that chemotherapy

Figure 8 Schistosoma haematobium infection trends within two separate sub-cohorts of schoolchildren that were followedup respectively between 2004 and 2005 (n = 795) and 2005—2006 (n = 883). Intensity of infection is measured as the geometric mean no. eggs/10 ml of urine. Error bars are 95% CI.

Piga Vita Kichocho on Unguja Island of exposure to contaminated environmental water bodies.17 Additionally, in future studies it may be useful to understand better the water-contact behaviour of adults and its repercussions for parasite transmission. Such behaviours are likely to include washing (of oneself and offspring) with, and working in or near, infected water sources (e.g. fishermen and farmers).

4.2. Dynamics of STHs STH infection markers showed more modest and even equivocal changes over the course of the control programme, which could be seen as disappointing. However, it is important to view the changes in a broader historical context, with dramatic reductions seen since the 1994 survey. One possible explanation for this marked decrease is the distribution of ivermectin and albendazole on both of Zanzibar’s islands by the Global Program to Eliminate Lymphatic Filariasis (GPELF). These drugs have been distributed to the entire population except children under five, pregnant women, women in the first week of breastfeeding after childbirth and severely ill people. Zanzibar has completed six rounds of annual mass treatment from 2001 to 2006, reaching the whole at-risk population and achieving therapeutic coverage levels in excess of 80%.32 As well as targeting Wuchereria bancrofti [the causative agent of lymphatic filariasis (LF) on Zanzibar], the distribution of albendazole is known to bring ancillary benefits as a broad-spectrum anthelminthic, while ivermectin also helps to treat A. lumbricoides and T. trichiura.33 It therefore seems likely that the GPELF has contributed to a reduction in STH infections to their current low levels and that the changes being presently observed represent much smaller perturbations to a generally decreasing trend. It may be that the levels of STH infection intensity and prevalence have reached the lowest levels possible from chemotherapy alone using a mass drug administration (MDA) approach. In China, where control of both ascariasis and LF has been successful, a targeted approach to treatment has followed MDA in order to push the parasite populations below their transmission breakpoints.34 Even so, the modest rise in A. lumbricoides infection prevalence and intensity levels from 2004 to 2006 is potentially worrying. Ascaris lumbricoides typically displays heaviest infection and greatest prevalence in individuals aged 5—10 years.35—37 The official age of entry into the school system is 6 years; however, in the current study, the median age of those children into the youngest year, Standard I, was 8 years. Therefore there is an age gap during which, if not treated in the community, those most at risk of A. lumbricoides infections and harbouring the heaviest burdens would not have been treated. Therefore including pre-school treatment for the control of STH infections is a strategy worth considering when implementing the integration of neglected tropical disease control,38 as albendazole can be administered to children younger than 5 years.39

4.3. Infection predisposition and polyparasitism From detailed analysis of treatment records, previously infected children were likely to have heavier infections

1041 at follow-up compared with non-infected children, as has been reported in other studies for S. haematobium40 and for STH.37,41 This relationship could be due to treatment failure or poor compliance, although this is unlikely given the reported high efficacy of praziquantel against S. haematobium10 and the use of treatment books to record those individuals who have received and taken the drugs. A more plausible explanation is that some individuals are predisposed to infection and reinfection via behavioural, genetic, immunological, nutritional or social factors, or combinations thereof. Further studies are needed to disentangle the contribution of each of these factors. Further, an ability to capture individual-level heterogeneity in transmission, infection and morbidity would aid the effective planning of disease control programmes and allow their course to be accurately predicted. A subset of children (or of the wider population) will be contributing most to transmission and be at greatest risk of infection and morbidity; clearly, it is important to identify this subset. Older schoolchildren were more likely to be infected with schistosomes, a pattern that has been described previously, whereby the intensity of schistosome infections reaches their peak at around age 15 years.35,42 There were significant associations between S. haematobium and T. trichiura and hookworm, corroborating earlier studies on helminth co-infections.3,43,44 . As has been previously reported,17,45 water-contact and water-contamination behaviours are strongly associated with schistosome infection, even after controlling for sex, because they allow greater opportunity for humans to become infected with schistosomal cercariae. Also, there is the possibility of schistosome-induced reductions in bladder size, which would increase the need to void and potentially increase the frequency of urinating in streams, thus aiding transmission. Working in fields and rice paddies is likely to increase not only water contact but also the contact with humid and possibly contaminated soil, enhancing opportunities for infection by STHs. Having access to clean fresh water was found to be strongly negatively associated with STH infection, even after controlling for schistosome infections. Abdominal pain was negatively associated with heavy Ascaris infection, which seems an anomalous result and is difficult to explain, but could be confounded by the relatively small numbers of heavy Ascaris infection at baseline.

4.4. Extrapolation of the Piga Vita Kichocho experience to other settings and integration of parasite control programmes The population of Zanzibar has been the focus of several control efforts over past decades and recent years, and has arguably received more anthelminthic chemotherapy than comparable neighbouring countries. Although this may limit somewhat the extrapolation of the success of this programme to other settings, our results should be able to help guide the direction of control efforts in other areas. This is particularly relevant given the presence of the GPELF intervention using a combination of ivermectin and albendazole against LF in other parts of Africa.46 The proposal for the integration of neglected tropical disease control has gained support and political momentum in recent years,

1042 with integrated programmes having started in some West and East African countries (by, among others, the Schistosomiasis Control Initiative). Understanding the impact of a schistosomiasis and STH control programme in the presence of other anti-parasitic vertical programmes will help inform decisions about the value of future integrated control strategies. Indeed, the first round of an integrated control programme took place on Unguja Island shortly after the end of the present study. The impact that this combination therapy has had on parasitological markers, and on the Kick out Kichocho programme, will be discussed elsewhere.

4.5. Other control strategies Chemotherapy plays a vital role in fighting infection and morbidity. However, it is clear that other approaches are also necessary in order to effect a profound and permanent impact on the transmission of these diseases. Although difficult to achieve, improvement of access to safe water supplies is crucial, and would have benefits in combating a myriad of other diseases. Health education leading to increased knowledge of the diseases among both children and adults, recognition of symptoms and opportune treatment, and changes in water-contact behaviour to avoid infection, are also important. As part of this programme, a health education booklet was introduced, entitled ‘Juma na Kichocho’, which provided health education messages, specific to schistosomiasis, in a child-friendly format. The results of a pilot project using this booklet have been discussed elsewhere,31 but in summary, it was found that there is a clear need for greater and more comprehensive health education for both children and adults in order to reinforce pertinent messages and induce appropriate behavioural changes in order to reduce infection markers. Besides, the heavy reliance on chemotherapy raises the issue of anthelminthic resistance,47,48 a problem that is widespread and well-recognized among nematode parasites of veterinary importance, but which should receive more attention during the implementation and monitoring of treatment programmes of humans.

5. Conclusion An integrated approach against urinary schistosomiasis and soil-transmitted helminthiases using praziquantel and albendazole, respectively, has been shown to be effective at reducing prevalence and intensity of infections in several countries in sub-Saharan Africa, as part of the Schistosomiasis Control Initiative,49,50 as well as other programmes.27,51 Deworming is now being integrated into other health packages such as national child health days for immunization, vitamin A distribution and measles vaccination programmes.52 This study provides further evidence that school-based deworming is effective at controlling schistosomiasis infection and morbidity, especially in low transmission areas. In high transmission areas other complementary methods of control at the local level are needed to synergise with chemotherapy to ensure that the beneficial impact of treatment is long-lasting, and to minimize the possibility of anthelminthic resistance spreading.

J.R. Stothard et al. Authors’ contributions: DR and JRS conceived and led the ‘Piga Vita Kichocho’ programme; JRS, ISK and DR designed, investigated and collected data during this project in association with the field staff at the Helminth Control Laboratory, Unguja; MDF and M-GB conducted the statistical analyses of the data as partial fulfillment for the MSc in Modern Epidemiology at Imperial College by MDF. All authors were involved in drafting the manuscript and have read and approved its final version. JRS and MDF are guarantors of the paper. Acknowledgements: We extend our sincere thanks to the schoolchildren, teachers and Shehias (community leaders) who helped in this investigation. We would like to acknowledge the important role of our late colleague and friend Mr Ali Foum Mgeni, who was tragically killed in a road traffic accident in December 2007, in the ‘Piga Vita Kichocho’ programme in Zanzibar. We are also grateful to the anonymous referees whose comments helped improve the manuscript. Funding: We are grateful for the financial assistance from the Health Foundation, UK and support from the Schistosomiasis Control Initiative, Imperial College London, UK and the African Development Bank, Tanzania. MDF and M-GB acknowledge the financial support of the Medical Research Council. The work has also benefited from support of the European Union (FP6 STREP CONTRAST project, contract no. 032203). Conflicts of interest: None declared. Ethical approval: This study was part of the islandwide parasitological surveys carried out in Unguja by the Helminth Control Laboratory and had the ethical approval of the Ministry of Health and Social Welfare, Zanzibar. The Review Board of the National Health Service Local Research Ethics Committee (application 03.36) of St Marys Hospital (London, UK) also approved the study on behalf of the Natural History Museum/Imperial College (London, UK).

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