Epidemiology and diagnosis of schistosomiasis in preschool-aged children in Azaguié, south Côte d'Ivoire

Coulibaly, Jean Tenena. Epidemiology and diagnosis of schistosomiasis in preschool-aged children in Azaguié, south Côte d'Ivoire. 2013, Doctoral Thesis, University of Basel, Faculty of Science.


Official URL: http://edoc.unibas.ch/diss/DissB_10434

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Background: Classified among the neglected tropical diseases (NTDs), schistosomiasis remains one of the most important parasitic diseases in the tropics and subtropics, and constitutes a major public health problem. Following World Health Assembly (WHA) resolution 54.19, put forth in May 2001, several control programmes have emerged in schistosomiasis-endemic countries with the objective to reduce morbidity due to schistosomiasis and soil-transmitted helminthiasis by regularly treating at least 75% and up to 100% of all school-aged children who are at risk by 2010. By focusing treatment upon the school-aged population, WHA resolution 54.19 neglects preschool-aged children, thus preventing them from benefiting from preventive chemotherapy targeted to their older peers, and hence creating a potential health inequity. Root causes include the belief that very young children would not yet be exposed to infected freshwater bodies, thus an insufficient understanding and documentation of the extent and severity of schistosomiasis in this age class, and a paucity of pharmacokinetic safety data of praziquantel among young children. However, in endemic zones, women are frequently accompanied by their children, even at young age, when they go to ponds, rivers or irrigation canals, all of which may be contaminated with cercariae, the infective stage to humans. Recent studies carried out in East and West Africa showed that intestinal and urogenital schistosomiasis can indeed occur in very early childhood. Pathology due to chronic infection with Schistosoma mansoni includes hepatic perisinusoidal egg granulomas, Symmers’ pipe-stem periportal fibrosis, portal hypertension and, occasionally, embolic egg granulomas in the brain or spinal cord. Schistosoma haematobium infection may cause haematuria, scarring, calcification, squamous cell carcinoma and, occasionally, embolic egg granulomas in the brain or spinal cord.
Goal and specific objectives: The overarching goal of this Ph.D. thesis is to deepen our understanding of the epidemiology of schistosomiasis in preschool-aged children. The thesis pursued five specific objectives in Azaguié district, south Côte d’Ivoire. First, to characterize intestinal parasitic infections at the Azaguié district level. Second, to assess the accuracy of a commercially available urine circulating cathodic antigen (CCA) cassette test (CCA-A) and an experimental formulation (CCA-B) for the diagnosis of S. mansoni among school-aged children in different endemicity settings. Third, to assess the accuracy of CCA-A for the diagnosis of S. mansoni in preschool-aged children before and after praziquantel administration. Fourth, to study the epidemiology and risk factors for schistosomiasis in preschool-aged children. Fifth, to assess the efficacy and safety of crushed praziquantel tablets in preschool-aged children in a co-endemic setting of S. mansoni and S. haematobium.
Methods: The fieldwork for this Ph.D. thesis was split into two parts. In order to address the first two objectives, in mid-2010, a cross-sectional study was carried out in seven schools from four locations of Azaguié district, including more than 600 schoolchildren. Multiple stool and urine samples were collected from each schoolchild over three consecutive days. Stool samples were examined with the Kato-Katz technique for the diagnosis of S. mansoni and soil-transmitted helminths (Trichuris trichiura, Ascaris lumbricoides and hookworm). Stool samples from the first day of collection were preserved in sodium acetate-acetic acid-formalin (SAF) and examined one month later using an ether-concentration method for the diagnosis of intestinal protozoa. Urine samples were examined with CCA tests (CCA-A on three days and CCA-B once) for the diagnosis of S. mansoni. In addition, urine samples were analysed with the urine filtration technique and reagent strips for the diagnosis of S. haematobium.
In order to address objectives 3-5, a cross-sectional study was implemented as a baseline survey in 2011 in two villages of Azaguié district, namely Azaguié Makouguié and Azaguié M’Bromé, where S. mansoni and S. haematobium coexist. About 300 preschool-aged children (<6 years) were involved in this study. Multiple stool and urine samples were collected over two consecutive days and subjected to the same laboratory procedures as the samples of the schoolchildren in 2010. Anthropometric measures (weight, height and arm circumference) and clinical features (temperature, haemoglobin level) from each preschool-aged child were recorded. Focus group discussions were performed with the mothers of the preschool-aged children and questionnaires administered for a risk factor assessment. Subsequently, preschool-aged children were treated with crushed praziquantel tablets and three weeks posttreatment, drug efficacy was determined following the same field and laboratory procedures as during the baseline study. Adverse events (within 3 and 24 hours posttreatment were recorded by interviewing the mothers of the preschoolers.
Results: The results of this PhD thesis can be structured as follows:
Intestinal parasitic infections in Azaguié: We showed that the selection of intervention settings by control programmes based on a single stool sample examined with duplicate Kato-Katz thick smears or a single urine sample subjected to a standard urine filtration method considerably underestimate the prevalence of Schistosoma infection. This led to a misclassification of intervention settings as defined by the World Health Organization (WHO) guidelines. Hence, in such a context, more sensitive diagnostic tools are needed to select the intervention settings with high accuracy. In addition, we found a small-scale heterogeneity in the distribution of helminth and intestinal protozoa infections. We also confirmed that polyparasitism is common in the Azaguié district.
Accuracy of urine CCA tests in different endemicity settings in schoolchildren: The prevalence of S. mansoni in the three different endemicity settings was 32.9%, 53.1% and 91.8%, respectively. In all three settings, the sensitivity of a single CCA-A test was similar to triplicate Kato-Katz thick smears and was 56.3% and 47.9% in setting A (S. mansoni prevalence, 32.9%), 69.6% and 73.9% in setting B (S. mansoni prevalence, 53.1%), and 89.6% and 94.2% in setting C (S. mansoni prevalence, 91.8%). The specificity of the CCA-A test was moderate (76.9–84.2%). The likelihood of a CCA-A test color reaction increased with higher S. mansoni faecal egg counts (odds ratio = 1.07, p <0.001). A concurrent S. haematobium infection or the presence of microhaematuria did not influence the CCA test results for S. mansoni diagnosis.
Accuracy of the urine CCA test in preschool-aged children: Before treatment, the prevalence of S. mansoni, as determined by quadruplicate Kato-Katz thick smears, duplicate CCA(t-) test considering “trace” as negative results, and CCA(t+) test with “trace” as positive, was 23.1%, 45.0% and 76.5%, respectively. Irrespectiv of the ‘gold’ standard, a single CCA test (CCA(t+) or CCA(t-)) was more sensitive than quadruplicate Kato-Katz thick smears before and after treatment. The specificity of a single CCA test ranged between 59.3% and 100% before and after treatment. The intensity of the CCA test band reaction was correlated with S. mansoni egg burden (odds ratio = 1.2, p = 0.04).
Epidemiology and risk factors of schistosomiasis in preschoolers: The prevalence of S. mansoni in preschool-aged children was 25.5% in Azaguié Makouguié and 21.6% in Azaguié M’Bromé and the prevalence of S. haematobium 17.3% and 5.9%, respectively. Most infections were of light intensity. Mothers’ occupation and older siblings played important roles in the epidemiology of schistosomiasis in preschool-aged children.
Efficacy and safety of crushed praziquantel in preschoolers: According to the Kato-Katz and urine filtration results, we found high efficacy of crushed praziquantel against S. mansoni (cure rate (CR) = 88.6%, egg reduction rate (ERR) = 96.7%) and S. haematobium (CR = 88.9%, ERR = 98.0%). Treatment was generally well tolerated, but moderate adverse events (i.e. body and face inflammation), which required close supervision by the study physician, were observed in four non-infected children.
Conclusions: More sensitive diagnostic tools and rigorous sampling approaches are needed to select schistosomiasis-endemicity settings with high accuracy. The observed small-scale heterogeneity of helminth and intestinal protozoa infections should be carefully considered by control programmes. A single urine CCA test is more sensitive than multiple Kato-Katz thick smears in school-aged as well as in preschool-aged children. The urine CCA test can be recommended for rapid identification of high risk communities. However, its application for monitoring the impact of control interventions needs further investigation. In our study settings, preschool-aged children are at risk of schistosomiasis and can be infected very early in childhood. Integrated control approaches including improvement of safe water supply, sanitation, health facilities, and health education are needed in our study communities. Crushed praziquantel is efficacious against S. mansoni and S. haematobium and can be recommended for the treatment of infected children at young age, but only if they are unambiguously diagnosed. Nevertheless, further research is needed to deepen our understanding on the safety of praziquantel in this age group.
Advisors:Utzinger, Jürg
Committee Members:Tanner, Marcel and Olliaro, Piero L.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Former Units within Swiss TPH > Health Impact Assessment (Utzinger)
UniBasel Contributors:Utzinger, Jürg and Tanner, Marcel
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:10434
Thesis status:Complete
Number of Pages:215 S.
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edoc DOI:
Last Modified:22 Apr 2018 04:31
Deposited On:29 Jul 2013 12:37

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